Author: "Institut National de la Transfusion Sanguine [Paris] (INTS)" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Institut National de la Transfusion Sanguine [Paris] (INTS)"' showing total 608 results

Start Over Author "Institut National de la Transfusion Sanguine [Paris] (INTS)"

608 results on '"Institut National de la Transfusion Sanguine [Paris] (INTS)"'

151. Modeling of a Cell-Free Synthetic System for Biohydrogen Production

Author: Frédéric Cadet, Nicolas Fontaine, Bernard Offmann, Brigitte Grondin-Perez, GARDEBIEN, Fabrice, Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Energy Lab (ENERGY Lab), Université de La Réunion (UR), Unité de fonctionnalité et ingénierie de protéines (UFIP), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Laboratoire d'Energétique, d'Electronique et Procédés (LE2P)
Subjects: Artificial neural network, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Hydrogen, Computer science, [SPI.GPROC] Engineering Sciences [physics]/Chemical and Process Engineering, chemistry.chemical_element, 02 engineering and technology, Cellobiose, 01 natural sciences, Synthetic biology, chemistry.chemical_compound, Component (UML), Production (economics), Biohydrogen, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Hydrogen production, 010405 organic chemistry, System optimization, 021001 nanoscience & nanotechnology, 0104 chemical sciences, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, Biochemical engineering, Cell-Free synthetic system, chemistry, Yield (chemistry), Mathematical modeling, 0210 nano-technology, Simulation
Abstract: International audience; Hydrogen is a good candidate for the next generation fuel with a high energy density and an environment friendly behavior in the energy production phase. Micro-organism based biological production of hydrogen currently suffers low hydrogen production yields because the living cells must sustain different cellular activities other than the hydrogen production to survive. To circumvent this, teams have explored the synthetic assembly of enzymes in-vitro in cell-free systems with specific functions. Such a synthetic cell-free system was recently devised by combining 13 different enzymes to synthesize hydrogen from cellulose or cellobiose with better yield than microorganism-based systems. We used methods based on differential equations calculations to investigate how the initial conditions and the kinetic parameters of the enzymes influenced the productivity of a such system and, through simulations, identified those conditions that would optimize hydrogen production starting with cellobiose as substrate. Further, if the kinetic parameters of the component enzymes of such a system are not known, we showed how, using artificial neural network, it is possible to identify alternative models that account for the rate of production of hydrogen. This work demonstrates how modeling can help in designing and characterizing cell-free systems in synthetic biology. A web-based simulator implementing our differential equations based model is provided freely as a service for noncommercial usage at http://www.bo-protscience.fr/h2.
Published: 2015

152. Toward Atomistic Resolution Structure of Phosphatidylcholine Headgroup and Glycerol Backbone at Different Ambient Conditions

Author: Waldemar Kulig, Alexander P. Lyubartsev, Luca Monticelli, Matej Kanduč, Patrick F.J. Fuchs, Hubert Santuz, Jukka Määttä, Joona Tynkkynen, Antti Lamberg, Fernando Favela-Rosales, Marius Retegan, Tomasz Róg, Matti Javanainen, Claire Loison, O. H. Samuli Ollila, Markus S. Miettinen, Alexandru Botan, Tampere University, Department of Physics, Research area: Computational Physics, Doctoral Programme in Engineering and Natural Sciences, Computational Science X (CompX), Institut Lumière Matière [Villeurbanne] (ILM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Departamento de Física, Centro de Investigación y de Estudios Avanzados del IPN, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Physics [Tampere], Tampere University of Technology [Tampere] (TUT), Fachbereich Physik [Berlin], Freie Universität Berlin, Kyoto University [Kyoto], Department of Materials and Environmental Chemistry, Stockholm University, Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Aalto University, Department of Neuroscience and Biomedical Engineering, Max Planck Institute for Chemical Energy Conversion, Max-Planck-Gesellschaft, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Institut National de la Transfusion Sanguine [Paris] (INTS), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Chemistry, and Aalto-yliopisto
Subjects: Glycerol, Proton Magnetic Resonance Spectroscopy, education, 01 natural sciences, 114 Physical sciences, Article, Turn (biochemistry), 03 medical and health sciences, Molecular dynamics, chemistry.chemical_compound, [SPI]Engineering Sciences [physics], Phosphatidylcholine, 0103 physical sciences, Organic compounds, Materials Chemistry, Molecule, [CHIM]Chemical Sciences, Physical and Theoretical Chemistry, Carbon-13 Magnetic Resonance Spectroscopy, Lipid bilayer, ta116, 030304 developmental biology, Nutrition, [PHYS]Physics [physics], 0303 health sciences, 010304 chemical physics, Molecular Structure, Resolution (electron density), Biological membrane, Lipids, Surfaces, Coatings and Films, Crystallography, chemistry, Solid-state nuclear magnetic resonance, Chemical physics, Alcohols, Phosphatidylcholines, Order
Abstract: Phospholipids are essential building blocks of biological membranes. Despite a vast amount of very accurate experimental data, the atomistic resolution structures sampled by the glycerol backbone and choline headgroup in phoshatidylcholine bilayers are not known. Atomistic resolution molecular dynamics simulations have the potential to resolve the structures, and to give an arrestingly intuitive interpretation of the experimental data, but only if the simulations reproduce the data within experimental accuracy. In the present work, we simulated phosphatidylcholine (PC) lipid bilayers with 13 different atomistic models, and compared simulations with NMR experiments in terms of the highly structurally sensitive C-H bond vector order parameters. Focusing on the glycerol backbone and choline headgroups, we showed that the order parameter comparison can be used to judge the atomistic resolution structural accuracy of the models. Accurate models, in turn, allow molecular dynamics simulations to be used as an interpretation tool that translates these NMR data into a dynamic three-dimensional representation of biomolecules in biologically relevant conditions. In addition to lipid bilayers in fully hydrated conditions, we reviewed previous experimental data for dehydrated bilayers and cholesterol-containing bilayers, and interpreted them with simulations. Although none of the existing models reached experimental accuracy, by critically comparing them we were able to distill relevant chemical information: (1) increase of choline order parameters indicates the P-N vector tilting more parallel to the membrane, and (2) cholesterol induces only minor changes to the PC (glycerol backbone) structure. This work has been done as a fully open collaboration, using nmrlipids.blogspot.fi as a communication platform; all the scientific contributions were made publicly on this blog. During the open research process, the repository holding our simulation trajectories and files (https://zenodo.org/collection/user-nmrlipids) has become the most extensive publicly available collection of molecular dynamics simulation trajectories of lipid bilayers. publishedVersion
Published: 2015

153. Modélisation de système synthétique pour la production de biohydrogène

Author: Fontaine, Nicolas, STAR, ABES, Energy Lab (ENERGY Lab), Université de La Réunion (UR), Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Université de la Réunion, Brigitte Grondin-Perez, and Bernard Offmann
Subjects: Artificial neural network, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], System optimization, Biologie synthétique acelluaire, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Biochemical engineering, Cell-Free synthetic system, Ingénierie biochimique, Hydrogen production, Production d'hydrogène, Réseau de neurones artificiels, Mathematical modeling, Modélisation mathématique, Simulation, Optimisation de système
Abstract: Hydrogen is a candidate for the next generation fuel with a high energy density and an environment friendly behavior in the energy production phase. Micro-organism based biological production of hydrogen currently suffers low hydrogen production yields because the living cells must sustain different cellular activities other than the hydrogen production to survive. To circumvent this, a team have designed a synthetic cell-free system by combining 13 different enzymes to synthesize hydrogen from cellobiose. This assembly has better yield than microorganism-based systems. We used methods based on differential equations calculations to investigate how the initial conditions and the kinetic parameters of the enzymes influenced the productivity of a such system and, through simulations, to identify those conditions that would optimize hydrogen production starting with cellobiose as substrate. Further, if the kinetic parameters of the component enzymes of such a system are not known, we showed how, using artificial neural network, it is possible to identify alternative models that allow to have an idea of the kinetics of hydrogen production. During our study on the system using cellobiose, other cell-free assemblies were engineered to produce hydrogen from different raw materials. Interested in the reconstruction of synthetic systems, we decided to conceive various tools to help the automation of the assembly and the modelling of these new synthetic networks. This work demonstrates how modeling can help in designing and characterizing cell-free systems in synthetic biology., L'épuisement annoncé dans les prochaines décennies des ressources fossiles qui fournissent actuellement plus de 70% du carburant consommé dans les transports terrestres, aériens et maritimes au niveau mondial, incite à l'identification et le développement de nouvelles sources d'énergies renouvelables. La production de biocarburants issue de l'exploitation de la biomasse représente une des voies de recherche les plus prometteuses. Si la première génération des biocarburants (production à partir de plantes sucrières, de céréales ou d'oléagineux) atteint ses limites (concurrence avec les usages alimentaires, en particulier), la deuxième génération, produite à partir de ressources carbonées non alimentaires (lignocellulosique, mélasse, vinasse...), pourrait prendre le relais, une fois que les procédés de conversion seront suffisamment maîtrisés. À plus long terme, une troisième génération pourrait voir le jour, qui reposerait sur l'exploitation de la biomasse marine (microalgues, en particulier) mais où de nombreux verrous restent toutefois à lever : optimisation des procédés de culture et de récolte, extraction à coût réduit, optimisation des voies métaboliques etc. Il est à retenir que la stratégie nationale de recherche et d'innovation (SNRI) a retenu quatre « domaines clés » pour l'énergie : le nucléaire, le solaire photovoltaïque, les biocarburants de deuxième génération et les énergies marines. Ceux-ci sont complétés, au nom de leur contribution potentielle à la lutte contre le changement climatique, par le stockage du CO2, la conversion de l'énergie (dont les piles à combustible) et l'hydrogène. Le présent projet de recherche s'intéresse à explorer des voies d'amélioration de l'efficacité de la biotransformation de matière organique non alimentaire de nature industrielle en biocarburants de deuxième génération. En particulier, on s'intéressera à deux aspects complémentaires : l'optimisation des organismes microbiens et des voies métaboliques pour l'amélioration du rendement biologique de fabrication de biocarburants ; l'optimisation des procédés de mise en culture des microorganismes et d'extraction des biocarburant. Le projet de thèse consiste à mettre en œuvre les biotechnologies blanches, la biologie de synthèse et le génie des procédés pour la caractérisation de souches bactériennes, de leurs voies métaboliques et de prototypes expérimentaux pour la fabrication de biocarburants, de méthane et d'hydrogène à partir de rejets provenant de l'industrie sucrière de La Réunion, à savoir la mélasse ou la vinasse. Ce projet permettrait d'envisager de nouvelles perspectives de valorisation pour ces déchets industriels et de participer à la construction, à terme, d'une industrie réunionnaise durable des biocarburants et de l'hydrogène.
Published: 2015

154. Use of a structural alphabet to find compatible folds for amino acid sequences

Author: Mahajan, Swapnil, De Brevern, Alexandre, Sanejouand, Yves-Henri, Srinivasan, Narayanaswamy, Offmann, Bernard, Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Laboratoire Joliot Curie, École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biochimie et Génétique Moléculaire (LBGM), Université de La Réunion (UR), Unité de fonctionnalité et ingénierie de protéines (UFIP), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS), and Université de Nantes - Faculté des Sciences et des Techniques
Subjects: Models, Molecular, Protein Folding, Methods and Applications, Protein Conformation, Sequence Analysis, Protein, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Molecular Sequence Data, Proteins, Amino Acid Sequence, Sequence Alignment, Algorithms, ComputingMilieux_MISCELLANEOUS
Abstract: The structural annotation of proteins with no detectable homologs of known 3D structure identified using sequence-search methods is a major challenge today. We propose an original method that computes the conditional probabilities for the amino-acid sequence of a protein to fit to known protein 3D structures using a structural alphabet, known as "Protein Blocks" (PBs). PBs constitute a library of 16 local structural prototypes that approximate every part of protein backbone structures. It is used to encode 3D protein structures into 1D PB sequences and to capture sequence to structure relationships. Our method relies on amino acid occurrence matrices, one for each PB, to score global and local threading of query amino acid sequences to protein folds encoded into PB sequences. It does not use any information from residue contacts or sequence-search methods or explicit incorporation of hydrophobic effect. The performance of the method was assessed with independent test datasets derived from SCOP 1.75A. With a Z-score cutoff that achieved 95% specificity (i.e., less than 5% false positives), global and local threading showed sensitivity of 64.1% and 34.2%, respectively. We further tested its performance on 57 difficult CASP10 targets that had no known homologs in PDB: 38 compatible templates were identified by our approach and 66% of these hits yielded correctly predicted structures. This method scales-up well and offers promising perspectives for structural annotations at genomic level. It has been implemented in the form of a web-server that is freely available at http://www.bo-protscience.fr/forsa.
Published: 2015

155. Simulations Meet Experiment to Reveal New Insights into DNA Intrinsic Mechanics

Author: Ben Imeddourene, Akli, Elbahnsi, Ahmad, Guéroult, Marc, Oguey, Christophe, Foloppe, Nicolas, Hartmann, Brigitte, Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique Théorique et Modélisation (LPTM - UMR 8089), Centre National de la Recherche Scientifique (CNRS)-CY Cergy Paris Université (CY), Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), University of Cambridge [UK] (CAM), and HAL-UPMC, Gestionnaire
Subjects: Structure-Activity Relationship, Base Sequence, Models, Chemical, QH301-705.5, Sequence Analysis, Protein, Molecular Sequence Data, Nucleic Acid Conformation, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology (General), Molecular Dynamics Simulation, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Research Article
Abstract: The accurate prediction of the structure and dynamics of DNA remains a major challenge in computational biology due to the dearth of precise experimental information on DNA free in solution and limitations in the DNA force-fields underpinning the simulations. A new generation of force-fields has been developed to better represent the sequence-dependent B-DNA intrinsic mechanics, in particular with respect to the BI ↔ BII backbone equilibrium, which is essential to understand the B-DNA properties. Here, the performance of MD simulations with the newly updated force-fields Parmbsc0εζOLI and CHARMM36 was tested against a large ensemble of recent NMR data collected on four DNA dodecamers involved in nucleosome positioning. We find impressive progress towards a coherent, realistic representation of B-DNA in solution, despite residual shortcomings. This improved representation allows new and deeper interpretation of the experimental observables, including regarding the behavior of facing phosphate groups in complementary dinucleotides, and their modulation by the sequence. It also provides the opportunity to extensively revisit and refine the coupling between backbone states and inter base pair parameters, which emerges as a common theme across all the complementary dinucleotides. In sum, the global agreement between simulations and experiment reveals new aspects of intrinsic DNA mechanics, a key component of DNA-protein recognition., Author Summary The ability to simulate computationally the structure and dynamics of biomolecules is a major goal of structural biology. Such simulations require the calculation of the forces and energy of the system, typically with extensively parametrized functions called “force-fields”. Developing reliable force-fields has been very challenging for DNA, mainly because the simulations have to reproduce subtle, complex, sequence-dependent differences that also remain difficult to capture experimentally in solution. Here, we take advantage of an extensive set of recent experimental (NMR) data gathered on selected DNA oligomers to test the performance of a new generation of force-fields for DNA simulations. Our results demonstrate impressive progress towards more realistic simulations of DNA. The agreement between experiment and simulations is now good enough to incite further interpretation of the experimental observables and yield new original insights into the intrinsic DNA mechanics. In sum, this work shows that reliable DNA simulations provide a much finer understanding of the structural and dynamical B-DNA behavior, which will be essential to account for DNA recognition by proteins.
Published: 2015

156. Erythropoietin enhances whole body lipid oxidation during prolonged exercise in humans

Author: Helmi Ben Saad, Jacques Mercier, Philippe Connes, Corinne Caillaud, MORNET, Dominique, The University of Sydney, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Université de Sousse, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie intégrée du globule rouge (BIGR), and Université des Antilles et de la Guyane (UAG)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, Physiology, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine.medical_treatment, 030209 endocrinology & metabolism, Hematocrit, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Lipid oxidation, Internal medicine, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Aerobic exercise, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Erythropoietin, Exercise, Saline, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.diagnostic_test, business.industry, VO2 max, 030229 sport sciences, General Medicine, Carbohydrate, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Lipid Metabolism, Recombinant Proteins, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Endocrinology, Hemoglobin, business, Oxidation-Reduction, medicine.drug
Abstract: Animal studies have suggested that erythropoietin, besides its well-known hematopoietic effects, can modulate metabolism and prevent fat accumulation. We investigated the effects of repeated injections of recombinant human erythropoietin (EPO) on the balance of substrate oxidation during aerobic exercise in humans. Twelve healthy aerobically trained males received subcutaneously either moderate dose of EPO (50 U/kg, EPO) or saline injections (NaCl 0.9 %, control) three times a week for 4 weeks. Body weight, % fat, maximal aerobic capacity, and substrate utilization during exercise were assessed before and after treatment, while hemoglobin and hematocrit were monitored regularly during the treatment. Carbohydrate and fat oxidation were evaluated via indirect calorimetry, during a submaximal exercise performed at 75 % of the participants’ maximal aerobic capacity ( $$ \overset{\cdotp }{V}{O}_{2 \max } $$ ) for 60 min. Results showed that 4 weeks of EPO treatment significantly enhanced fat oxidation (+56 % in EPO versus −9 % in control) during exercise, independent of its effects on hematological parameters or $$ \overset{\cdotp }{V}{O}_{2 \max } $$ . This study shows that EPO can modulate substrate utilization during exercise, leading to enhanced fat utilization and lower use of carbohydrates. This opens new research directions exploring whether systemic EPO levels, in physiological conditions, participate to the modulation of fat oxidation.
Published: 2015

157. Red blood cell proteomics reveal remnant protein biosynthesis and folding pathways in PIEZO1-related hereditary xerocytosis

Author: Alexis Caulier, Nicolas Jankovsky, Emilie Fleur Gautier, Wassim El Nemer, Corinne Guitton, Hakim Ouled-Haddou, François Guillonneau, Patrick Mayeux, Virginie Salnot, Johanna Bruce, Véronique Picard, Loïc Garçon, CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Plateforme protéomique 3P5 [Institut Cochin] (3P5), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Bicêtre, Université Paris-Saclay, and DESSAIVRE, Louise
Subjects: piezo1 channel, proteomics, xeroxytosis, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Physiology, Physiology (medical), ubiquitin, red blood cell, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Hereditary xerocytosis is a dominant red cell membrane disorder characterized by an increased leak of potassium from the inside to outside the red blood cell membrane, associated with loss of water leading to red cell dehydration and chronic hemolysis. 90% of cases are related to heterozygous gain of function mutations in PIEZO1, encoding a mechanotransductor that translates a mechanical stimulus into a biological signaling. Data are still required to understand better PIEZO1-HX pathophysiology. Recent studies identified proteomics as an accurate and high-input tool to study erythroid progenitors and circulating red cell physiology. Here, we isolated red blood cells from 5 controls and 5 HX patients carrying an identified and pathogenic PIEZO1 mutation and performed a comparative deep proteomic analysis. A total of 603 proteins were identified among which 56 were differentially expressed (40 over expressed and 16 under expressed) between controls and HX with a homogenous expression profile within each group. We observed relevant modifications in the protein expression profile related to PIEZO1 mutations, identifying two main “knots”. The first contained both proteins of the chaperonin containing TCP1 complex involved in the assembly of unfolded proteins, and proteins involved in translation. The second contained proteins involved in ubiquitination. Deregulation of proteins involved in protein biosynthesis was also observed in in vitro-produced reticulocytes after Yoda1 exposure. Thus, our work identifies significant changes in the protein content of PIEZO1-HX erythrocytes, revealing a “PIEZO1 signature” and identifying potentially targetable pathways in this disease characterized by a heterogeneous clinical expression and contra-indication of splenectomy.
Published: 2022

158. Characterization of hepatitis B viral forms from patient plasma using velocity gradient: Evidence for an excess of capsids in fractions enriched in Dane particles

Author: Charlotte Pronier, Jérémy Bomo, Juliette Besombes, Valentine Genet, Syria Laperche, Philippe Gripon, Vincent Thibault, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut National de la Transfusion Sanguine [Paris] (INTS), and Chard-Hutchinson, Xavier
Subjects: [SDV] Life Sciences [q-bio], Hepatitis B virus, Capsid, Hepatitis B Surface Antigens, Hepatitis B, Chronic, Multidisciplinary, Iohexol, [SDV]Life Sciences [q-bio], DNA, Viral, Humans, Reproducibility of Results, Hepatitis B e Antigens, Hepatitis B
Abstract: International audience; Hepatitis B virus (HBV) morphogenesis is characterized by a large over-production of subviral particles and recently described new forms in parallel of complete viral particles (VP). This study was designed to depict circulating viral forms in HBV infected patient plasmas, using velocity gradients and most sensitive viral markers. Plasmas from chronic hepatitis B (CHB) patients, HBeAg positive or negative, genotype D or E, were fractionated on velocity and equilibrium gradients with or without detergent treatment. Antigenic and molecular markers were measured in plasma and in each collected fraction. Fast Nycodenz velocity gradients revealed good reproducibility and provided additional information to standard equilibrium sucrose gradients. HBV-RNAs circulated as enveloped particles in all plasmas, except one, and at lesser concentrations than VP. Calculations based on standardized measurements and relative virion and subviral particle molecular stoichiometry allowed to refine the experimental approach. For the HBeAg-positive plasma, VP were accompanied by an overproduction of enveloped capsids, either containing HBs, likely corresponding to empty virions, or for the main part, devoid of this viral envelope protein. Similarly, in the HBeAg-negative sample, HBs enveloped capsids, likely corresponding to empty virions, were detected and the presence of enveloped capsids devoid of HBs protein was suspected but not clearly evidenced due to the presence of contaminating high-density subviral particles. While HBeAg largely influences HBcrAg measurement and accounts for two-thirds of HBcrAg reactivity in HBeAg-positive patients, it remains a 10 times more sensitive marker than HBsAg to characterize VP containing fractions. Using Nycodenz velocity gradients and standardized biomarkers, our study proposes a detailed characterization of circulating viral forms in chronically HBV infected patients. We provide evidence for an excess of capsids in fractions enriched in Dane particles, likely due to the presence of empty virions but also by capsids enveloped by an HBs free lipid layer. Identification of this new circulating viral particle sets the basis for studies around the potential role of these entities in hepatitis B pathogeny and their physiological regulation.
Published: 2022

159. A web-based tool for rational screening of mutants libraries using ProSAR

Author: Magali Remaud-Simeon, Philippe Charton, Magali Berland, Bernard Offmann, Isabelle André, Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Région Réunion, Fond Social Europeen (20100017), Région Pays de la Loire for ReMSIP project (2012-7279-7281), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Charton, Philippe, and Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Proteomics, epistatic interactions between mutations, Computer science, In silico, rational screening, Bioengineering, Computational biology, Bioinformatics, Biochemistry, Software, sequence-activity relationship, Web application, Databases, Protein, Molecular Biology, Gene Library, Internet, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], business.industry, Statistical model, protein engineering, Directed evolution, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], fitness landscape exploration, Mutation, Mutation (genetic algorithm), Regression Analysis, The Internet, Directed Molecular Evolution, business, Algorithms, Biotechnology
Abstract: International audience; In directed evolution experiments, it is at stake to have methods to screen efficiently the mutant libraries. We propose a web-based tool that implements an established in silico method for the rational screening of mutant libraries. The method, known as ProSAR, attempts to link sequence data to activity. The method uses statistical models trained on small experimental datasets provided by the user. These can integrate potential epistatic interactions between mutations and be used in many diverse biological contexts. It drastically improves the search for leading mutants. The tool is freely available to non-commercial users at http://bo-protscience.fr/prosar/.
Published: 2014

160. Construction and validation of an atomic model for bacterial TSPO from electron microscopy density, evolutionary constraints, and biochemical and biophysical data

Author: Catherine Etchebest, Mariano A. Ostuni, Konrad Hinsen, Aurore Vaitinadapoule, Jean-Jacques Lacapère, Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), and Frapart, Isabelle
Subjects: Models, Molecular, Molecular Sequence Data, Biophysics, Protoporphyrins, Rhodobacter sphaeroides, Biology, Transporter, Ligands, Biochemistry, Protein Structure, Secondary, chemistry.chemical_compound, Bacterial Proteins, Atomic model, Amino Acid Sequence, Conserved Sequence, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], chemistry.chemical_classification, Binding Sites, Cryoelectron Microscopy, Cell Biology, Ligand (biochemistry), biology.organism_classification, Isoquinolines, Transmembrane protein, Amino acid, Translocase 18kDa, Transmembrane domain, Monomer, Cholesterol, chemistry, Membrane protein, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Protein Multimerization, Carrier Proteins, Crystallization, Sequence Alignment, Protein Binding
Abstract: International audience; The 18kDa protein TSPO is a highly conserved transmembrane protein found in bacteria, yeast, animals and plants. TSPO is involved in a wide range of physiological functions, among which the transport of several molecules. The atomic structure of monomeric ligand-bound mouse TSPO in detergent has been published recently. A previously published low-resolution structure of Rhodobacter sphaeroides TSPO, obtained from tubular crystals with lipids and observed in cryo-electron microscopy, revealed an oligomeric structure without any ligand. We analyze this electron microscopy density in view of available biochemical and biophysical data, building a matching atomic model for the monomer and then the entire crystal. We compare its intra- and inter-molecular contacts with those predicted by amino acid covariation in TSPO proteins from evolutionary sequence analysis. The arrangement of the five transmembrane helices in a monomer of our model is different from that observed for the mouse TSPO. We analyze possible ligand binding sites for protoporphyrin, for the high-affinity ligand PK 11195, and for cholesterol in TSPO monomers and/or oligomers, and we discuss possible functional implications.
Published: 2014

161. mulPBA: an efficient multiple protein structure alignment method based on a structural alphabet

Author: Alexandre G. de Brevern, Sylvain Leonard, Agnel Praveen Joseph, Jean-Christophe Gelly, Narayanaswamy Srinivasan, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), GR-Ex, Laboratoire d'Excellence, GR-Ex, Molecular Biophysics Unit, Indian Institute of Science, Indo-French collaborative grant (CEFIPRA/IFCPAR 3903-E) The Ministry of Research (France) The University Paris Diderot, Sorbonne Paris Cite (France) The National Institute of Blood Transfusion (INTS, France) The National Institute of Health and Medical Research (INSERM, France) The Laboratories of Excellence, GR-Ex (France) Department of Biotechnology (India), and de Brevern, Alexandre G.
Subjects: Models, Molecular, Web server, Protein Conformation, Computer science, Structural alignment, MESH: Sequence Alignment, computer.software_genre, webserver, 03 medical and health sciences, MESH: Software, MESH: Protein Conformation, Structural Biology, Iterative refinement, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Proteins, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Loop modeling, protein conformations, protein superimposition, Molecular Biology, Java applet, 030304 developmental biology, Internet, 0303 health sciences, Multiple sequence alignment, 030302 biochemistry & molecular biology, Computational Biology, Proteins, General Medicine, computer.file_format, Protein structure prediction, Protein Data Bank, Crystallography, MESH: Internet, protein structures, Protein Blocks, structural alphabet, Sequence Alignment, computer, Algorithm, Software, MESH: Models, Molecular, MESH: Computational Biology
Abstract: International audience; The increasing number of available protein structures requires efficient tools for multiple structure comparison. Indeed, multiple structural alignments are essential for the analysis of function, evolution and architecture of protein structures. For this purpose, we proposed a new web server called multiple Protein Block Alignment (mulPBA). This server implements a method based on a structural alphabet to describe the backbone conformation of a protein chain in terms of dihedral angles. This 'sequence-like' representation enables the use of powerful sequence alignment methods for primary structure comparison, followed by an iterative refinement of the structural superposition. This approach yields alignments superior to most of the rigid-body alignment methods and highly comparable with the flexible structure comparison approaches. We implement this method in a web server designed to do multiple structure superimpositions from a set of structures given by the user. Outputs are given as both sequence alignment and superposed 3D structures visualized directly by static images generated by PyMol or through a Jmol applet allowing dynamic interaction. Multiple global quality measures are given. Relatedness between structures is indicated by a distance dendogram. Superimposed structures in PDB format can be also downloaded, and the results are quickly obtained. mulPBA server can be accessed at www.dsimb.inserm.fr/dsimb_tools/mulpba/ .
Published: 2014

162. Coarse-Grained Simulations of the HIV-1 Matrix Protein Anchoring: Revisiting Its Assembly on Membrane Domains

Author: Laurent Chaloin, Nicolas Floquet, Patrick F.J. Fuchs, Cyril Favard, Jean Martinez, Landry Charlier, Delphine Muriaux, Maxime Louet, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Institut de Recherche en Infectiologie de Montpellier (IRIM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS)
Subjects: Phosphatidylinositol 4,5-Diphosphate, Vesicle-associated membrane protein 8, HIV Antigens, Molecular Sequence Data, Biophysics, Molecular Dynamics Simulation, Biology, gag Gene Products, Human Immunodeficiency Virus, 7. Clean energy, Cell membrane, Viral envelope, medicine, Humans, Amino Acid Sequence, Lipid bilayer, Myristoylation, Host cell membrane, Membranes, Viral matrix protein, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Cell Membrane, Membrane, medicine.anatomical_structure, Biochemistry, Protein Binding
Abstract: International audience; In the accepted model for human immunodeficiency virus preassembly in infected host cells, the anchoring to the intracellular leaflet of the membrane of the matrix domain (MA) that lies at the N-terminus of the viral Gag protein precursor appears to be one of the crucial steps for particle assembly. In this study, we simulated the membrane anchoring of human immunodeficiency virus-1 myristoylated MA protein using a coarse-grained representation of both the protein and the membrane. Our calculations first suggest that the myristoyl group could spontaneously release from its initial hydrophobic pocket before MA protein interacts with the lipid membrane. All-atom simulations confirmed this possibility with a related energy cost estimated to be ∼5 kcal.mol−1. The phosphatidylinositol (4,5) bisphosphate (PI(4,5)P2) head binds preferentially to the MA highly basic region as described in available NMR data, but interestingly without flipping of its 2′ acyl chain into the MA protein. Moreover, MA was able to confine PI(4,5)P2 lipids all around its molecular surface after having found a stable orientation at the membrane surface. Our results suggest that this orientation is dependent on Myr anchoring and that this confinement induces a lateral segregation of PI(4,5)P2 in domains. This is consistent with a PI(4,5)P2 enrichment of the virus envelope as compared to the host cell membrane.
Published: 2014

163. Structure-Affinity Properties of a High-Affinity Ligand of FKBP12 Studied by Molecular Simulations of a Binding Intermediate

Author: Lilian Olivieri, Fabrice Gardebien, GARDEBIEN, Fabrice, Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), and Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: lcsh:Medicine, Tacrolimus Binding Protein 1A, Molecular Dynamics Simulation, Biology, Ligands, 010402 general chemistry, Bioinformatics, Biochemistry, 01 natural sciences, Protein Structure, Secondary, Structure-Activity Relationship, 03 medical and health sciences, Molecular dynamics, Protein structure, Biochemical Simulations, Intermediate state, Biomacromolecule-Ligand Interactions, Binding site, lcsh:Science, 030304 developmental biology, 0303 health sciences, Binding Sites, Multidisciplinary, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Ligand, Hydrogen bond, lcsh:R, Intermolecular force, Biology and Life Sciences, Computational Biology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 0104 chemical sciences, Crystallography, Intramolecular force, lcsh:Q, Protein Binding, Research Article
Abstract: International audience; With a view to explaining the structure-affinity properties of the ligands of the protein FKBP12, we characterized a binding intermediate state between this protein and a high-affinity ligand. Indeed, the nature and extent of the intermolecular contacts developed in such a species may play a role on its stability and, hence, on the overall association rate. To find the binding intermediate, a molecular simulation protocol was used to unbind the ligand by gradually decreasing the biasing forces introduced. The intermediate was subsequently refined with 17 independent stochastic boundary molecular dynamics simulations that provide a consistent picture of the intermediate state. In this state, the core region of the ligand remains stable, notably because of the two anchoring oxygen atoms that correspond to recurrent motifs found in all FKBP12 ligand core structures. Besides, the non-core regions participate in numerous transient intermolecular and intramolecular contacts. The dynamic aspect of most of the contacts seems important both for the ligand to retain at least a part of its configurational entropy and for avoiding a trapped state along the binding pathway. Since the transient and anchoring contacts contribute to increasing the stability of the intermediate, as a corollary, the dissociation rate constant k {1 of this intermediate should be decreased, resulting in an increase of the affinity constant K a. The present results support our previous conclusions and provide a coherent rationale for explaining the prevalence in high-affinity ligands of (i) the two oxygen atoms found in carbonyl or sulfonyl groups of dissimilar core structures and of (ii) symmetric or pseudo-symmetric mobile groups of atoms found as non-core moieties. Another interesting aspect of the intermediate OPEN ACCESS Citation: Olivieri L, Gardebien F (2014) Structure-Affinity Properties of a High-Affinity Ligand of FKBP12 Studied by Molecular Simulations of a Binding Intermediate. PLoS ONE 9(12): e114610.
Published: 2014

164. Ultradeep Pyrosequencing and Molecular Modeling Identify Key Structural Features of Hepatitis B Virus RNase H, a Putative Target for Antiviral Intervention

Author: Jean-Michel Pawlotsky, Georgios Germanidis, Christophe Rodriguez, Juliette Hayer, Christophe Combet, Fabien Zoulim, Gilbert Deléage, Bases moléculaires et structurales des systèmes infectieux ( BMSSI ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Centre National de Référence Virus des hépatites B, C et Delta, Institut National de la Transfusion Sanguine [Paris] ( INTS ) -Assistance publique - Hôpitaux de Paris (AP-HP), Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Pathology Clinic, Aristotle University of Thessaloniki-Papageorgiou General Hospital, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service Hépatologie, Hospices Civils de Lyon ( HCL ), J.H. received a doctoral fellowship from the Ministère de l'Enseignement Supérieur et de la Recherche (contract 0012). C.R. received a doctoral fellowship from the National Agency for Research on AIDS and Viral Hepatitis (ANRS). This work was supported by the Finovi Foundation (contract 051274 2010-2011), Fondation pour la Recherche Médicale (FRM), and the ANRS. Sequence data analyses and molecular modeling were performed on the PRABI computing platform (contract GIS-IBiSA 2009-2011)., Bases moléculaires et structurales des systèmes infectieux (BMSSI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Guellaen, Georges
Subjects: Models, Molecular, Hepatitis B virus, Genotype, Immunology, Population, Molecular Sequence Data, Ribonuclease H, Biology, medicine.disease_cause, Microbiology, Antiviral Agents, Hepatitis B virus PRE beta, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Virology, Vaccines and Antiviral Agents, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, RNase H, education, Gene, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Genetics, 0303 health sciences, education.field_of_study, Sequence Homology, Amino Acid, RNA, High-Throughput Nucleotide Sequencing, digestive system diseases, 3. Good health, HBx, chemistry, Insect Science, biology.protein, 030211 gastroenterology & hepatology, DNA
Abstract: Last-generation nucleoside/nucleotide analogues are potent against hepatitis B virus (HBV) and have a high barrier to resistance. However, delayed responses have been observed in patients previously exposed to other drugs of the same class, long-term resistance is possible, and cure of infection cannot be achieved with these therapies, emphasizing the need for alternative therapeutic approaches. The HBV RNase H represents an interesting target because its enzyme activity is essential to the HBV life cycle. The goal of our study was to characterize the structure of the HBV RNase H by computing a 3-dimensional molecular model derived from E. coli RNase H and analyzing 2,326 sequences of all HBV genotypes available in public databases and 958,000 sequences generated by means of ultradeep pyrosequencing of sequences from a homogenous population of 73 treatment-naive patients infected with HBV genotype D. Our data revealed that (i) the putative 4th catalytic residue displays unexpected variability that could be explained by the overlap of the HBx gene and has no apparent impact on HBV replicative capacity and that (ii) the C-helix-containing basic protrusion, which is required to guide the RNA/DNA heteroduplex into the catalytic site, is highly conserved and bears unique structural properties that can be used to target HBV-specific RNase H inhibitors without cross-species activity. The model shows substantial differences from other known RNases H and paves the way for functional and structural studies as a prerequisite to the development of new inhibitors of the HBV cell cycle specifically targeting RNase H activity.
Published: 2014

165. Correlation between local structural dynamics of proteins inferred from NMR ensembles and evolutionary dynamics of homologues of known structure

Author: Mahajan, Swapnil, De Brevern, Alexandre, Offmann, Bernard, Srinivasan, Narayanaswamy, Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), GR-Ex, Laboratoire d'Excellence, GR-Ex, Université de La Réunion - Faculté des Sciences et Technologies (FST), Université de La Réunion (UR), Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Unité de fonctionnalité et ingénierie de protéines (UFIP), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), MBU, Molecular Biophysics Unit, Indian Institute of Science-Indian Institute of Science, SM is supported by PhD scholarship grant from Fonds Européen de Dévelopment Régional and Conseil Regional de La Réunion [20100079, Tiers: 144645]. This research is also supported by Indo-French collaborative grant (CEFIPRA/IFCPAR 3903-E) to NS and AdB. This work was supported by grants from the Ministry of Research (France), University of Paris Diderot, Sorbonne Paris Cité (France), National Institute for Blood Transfusion (INTS, France), Institute for Health and Medical Research (INSERM, France) to AdB, and University of Nantes (France) and Conseil Régional Pays de La Loire (France) to BO and Department of Biotechnology (India) to NS.
Subjects: Quantitative Biology::Biomolecules, flexibility, substitution matrix, statistics, evolution, Protein Blocks, structural variation, conservation, structural alphabet, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], NMR
Abstract: International audience; Conformational changes in proteins are extremely important for their biochemical functions. Correlation between inherent conformational variations in a protein and conformational differences in its homologues of known structure is still unclear. In this study, we have used a structural alphabet called Protein Blocks (PBs). PBs are used to perform abstraction of protein 3-D structures into a 1-D strings of 16 alphabets (a-p) based on dihedral angles of overlapping pentapeptides. We have analyzed the variations in local conformations in terms of PBs represented in the ensembles of 801 protein structures determined using NMR spectroscopy. In the analysis of concatenated data over all the residues in all the NMR ensembles, we observe that the overall nature of inherent local structural variations in NMR ensembles is similar to the nature of local structural differences in homologous proteins with a high correlation coefficient of .94. High correlation at the alignment positions corresponding to helical and β-sheet regions is only expected. However, the correlation coefficient by considering only the loop regions is also quite high (.91). Surprisingly, segregated position-wise analysis shows that this high correlation does not hold true to loop regions at the structurally equivalent positions in NMR ensembles and their homologues of known structure. This suggests that the general nature of local structural changes is unique; however most of the local structural variations in loop regions of NMR ensembles do not correlate to their local structural differences at structurally equivalent positions in homologues.
Published: 2014

166. Correlation between local structural dynamics of proteins inferred from NMR ensembles and evolutionary dynamics of homologues of known structure.: Inherent and evolutionary structural dynamics

Author: Mahajan, Swapnil, de Brevern, Alexandre, Offmann, Bernard, Srinivasan, Narayanaswamy, Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), GR-Ex, Laboratoire d'Excellence, GR-Ex, Université de La Réunion - Faculté des Sciences et Technologies (FST), Université de La Réunion (UR), Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Unité de fonctionnalité et ingénierie de protéines (UFIP), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), MBU, Molecular Biophysics Unit, Indian Institute of Science-Indian Institute of Science, SM is supported by PhD scholarship grant from Fonds Européen de Dévelopment Régional and Conseil Regional de La Réunion [20100079, Tiers: 144645]. This research is also supported by Indo-French collaborative grant (CEFIPRA/IFCPAR 3903-E) to NS and AdB. This work was supported by grants from the Ministry of Research (France), University of Paris Diderot, Sorbonne Paris Cité (France), National Institute for Blood Transfusion (INTS, France), Institute for Health and Medical Research (INSERM, France) to AdB, University of Nantes (France) and Conseil Régional Pays de La Loire (France) to BO and Department of Biotechnology (India) to NS., and de Brevern, Alexandre G.
Subjects: Quantitative Biology::Biomolecules, substitution matrix, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], structural variation, conservation, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], NMR, flexibility, statistics, evolution, Protein Blocks, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, structural alphabet, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract: International audience; Conformational changes in proteins are extremely important for their biochemical functions. Correlation between inherent conformational variations in a protein and conformational differences in its homologues of known structure is still unclear. In this study, we have used a structural alphabet called Protein Blocks (PBs). PBs are used to perform abstraction of protein 3-D structures into a 1-D strings of 16 alphabets (a-p) based on dihedral angles of overlapping pentapeptides. We have analyzed the variations in local conformations in terms of PBs represented in the ensembles of 801 protein structures determined using NMR spectroscopy. In the analysis of concatenated data over all the residues in all the NMR ensembles, we observe that the overall nature of inherent local structural variations in NMR ensembles is similar to the nature of local structural differences in homologous proteins with a high correlation coefficient of .94. High correlation at the alignment positions corresponding to helical and β-sheet regions is only expected. However, the correlation coefficient by considering only the loop regions is also quite high (.91). Surprisingly, segregated position-wise analysis shows that this high correlation does not hold true to loop regions at the structurally equivalent positions in NMR ensembles and their homologues of known structure. This suggests that the general nature of local structural changes is unique; however most of the local structural variations in loop regions of NMR ensembles do not correlate to their local structural differences at structurally equivalent positions in homologues.
Published: 2014

167. Resolution of chronic hepatitis Delta after 1 year of combined therapy with pegylated interferon, tenofovir and emtricitabine

Author: Françoise Lunel, Adeline Pivert, Frédéric Le Gal, Alexandra Ducancelle, Paul Calès, Wael Y. Mansour, Pierre Abgueguen, Emmanuel Gordien, Hélène Le Guillou-Guillemette, Centre national de référence des virus des hépatites B, C et Delta, Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Groupe hospitalier Henri-Mondor, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Service des maladies infectieuses et tropicales [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Université Paris 13 (UP13)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe hospitalier Henri-Mondor
Subjects: Male, HBsAg, Hepatitis D, Chronic, [SDV]Life Sciences [q-bio], Organophosphonates, Interferon alpha-2, Antibodies, Viral, Emtricitabine, Antiviral Agents, Deoxycytidine, Polyethylene Glycols, 03 medical and health sciences, 0302 clinical medicine, Tenofovir disoproxil fumarate, Pegylated interferon, Virology, Humans, Medicine, Tenofovir, Chronic hepatitis Delta, 030304 developmental biology, Hepatitis, 0303 health sciences, business.industry, Adenine, Seroconversion anti-HBs, Interferon-alpha, virus diseases, Middle Aged, Hepatitis B, medicine.disease, Hepatitis D, Recombinant Proteins, 3. Good health, Treatment Outcome, Infectious Diseases, HBeAg, DNA, Viral, RNA, Viral, Drug Therapy, Combination, 030211 gastroenterology & hepatology, Hepatitis Delta Virus, business, Viral load, medicine.drug
Abstract: International audience; BackgroundHepatitis Delta virus (HDV) Infection has a worldwide distribution, with approximately 20 millions infected persons. Interferon (IFN) is the only approved drug for the treatment of HDV infection which is still a difficult to treat disease. Objectives To report a successful treatment of a patient with a chronic severe hepatitis Delta using combination therapy with Pegylated interferon (PegIFN), Tenofovir disoproxil fumarate (TDF) and Emtricitabine (FTC). Study Design The patient, a 47 years -old male patient, originating from Dagestan (East Asia), suffered of chronic hepatitis Delta infection. The patient was HBsAg, HBeAg, and anti-Delta Ab (IgG) positive. Serum HBV-DNA level was elevated (more than 9 logUI/mL). Serum HDV-RNA level was up to 5.6 log (copies/ml). Genotypes HBV/D and HDV-1 were demonstrated. The liver histology revealed chronic active hepatitis (Metavir score: A2F2). The treatment was started with PegIFN (180 μg/week) for two months and then TDF (300 mg/day) (combined later with FTC) was added. Results Sustained response was obtained after 10 months of treatment and was accompanied by the clearance of serum hepatitis B virus surface antigen with seroconversion to anti-HBs. Conclusion This case report suggests that Delta infection may co-exist with high replicative HBV infection and that combination therapy with PegIFN and nucleoside/tide analogues seems to be more effective than IFN alone. Given that only a single case is reported, further studies including more patients are warranted.
Published: 2010

168. Exploration de la reconnaissance de la courbure membranaire par le motif ALPS

Author: Vamparys, Lydie, Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Diderot - Paris VII, Dr. Patrick Fuchs et Pr. Catherine Etchebest(patrick.fuchs@univ-paris-diderot.fr et catherine.etchebest@univ-paris-diderot.fr), Vamparys, Lydie, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS)
Subjects: [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Vesicular transport, Interaction peptide-membrane, Molecular Modeling, Transport vésiculaire, Structure et dynamique des membranes, Insertion et repliement de peptides, Membrane curvature, Courbure membranaire, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Simulations de dynamique moléculaire, Insertion and folding of peptides, Structure and dynamics of membranes, [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, Molecular Dynamics simulations, Membrane lipids, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Peptide-membrane interaction, Modélisation moléculaire, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], Lipides membranaires
Abstract: Some biological processes such as vesicular transport are regulated by motifs that guide proteins to curved membranes. One of them is the ALPS (Amphipathic Lipid Packing Sensor) motif that recognizes packing defects induced by the convex curvature of the membrane. In this work, we combine molecular dynamics (MD) simulations and circular dichroism (CD) experiments to understand this phenomenon at the molecular level. MD simulations allowed us to characterize and quantify lipid packing defects. We show that packing defects caused by the membrane curvature are similar to those caused by the introduction of conical lipids in a flat bilayer composed of cylindrical lipids. By examining the interaction of the ALPS motif with a membrane containing such defects, we show that the early insertion of this motif on the membrane surface is driven by the inserton of its bulky hydrophobic residues in pre-existing defects. CD experiments and replica exchange MD simulations indicate that defects facilitate the ALPS folding into a partial alpha-helix. Finally, CD experiments allowed us to explore the thermodynamics of ALPS motif insertion as a function of lipid composition. Our work suggests that the peculiar amino-acid composition of the ALPS motif, as well as, its low helicity play a role in the recognition of packing defects, therefore curvature., Certains processus biologiques tels que le transport vésiculaire sont régulés par des motifs qui guident les protéines vers les membranes courbées. L'un d'entre eux est le motif ALPS (Amphipathic Lipid Packing Sensor) qui reconnaît les défauts de packing provoqués par la courbure convexe de la membrane. Dans ce travail, nous combinons des simulations de dynamique moléculaire (DM) et des expériences de dichroïsme circulaire (CD) pour comprendre ce phénomène à l'échelle moléculaire. Les simulations de DM nous ont permis de caractériser et de quantifier les défauts de packing entre les lipides. Nous montrons que les défauts de packing provoqués par la courbure membranaire sont similaires à ceux provoqués par l'introduction de lipides coniques dans une bicouche plate composée de lipides cylindriques. En examinant l'interaction du motif ALPS avec une membrane contenant de tels défauts, nous montrons que l'insertion précoce de ce motif à la membrane est guidée par l'insertion de ses gros résidus hydrophobes dans des défauts pré-existants. Les expériences de CD et les simulations de DM avec échanges de répliques indiquent que les défauts facilitent le repliement du motif ALPS en une hélice alpha partielle. Enfin, les expériences de CD nous ont permis d'explorer la thermodynamique d'insertion du motif ALPS en fonction de la composition lipidique. Notre travail suggère que la composition de séquence particulière du motif ALPS ainsi que son faible taux d'hélicité jouent un rôle dans la reconnaissance des défauts de packing, donc de la courbure.
Published: 2013

169. Erythrocytic vacuoles that accumulate a fluorescent dye predict spleen size and function in sickle cell disease

Author: Abdoulaye Sissoko, Aurélie Fricot‐Monsinjon, Camille Roussel, Sandra Manceau, Lucie Dumas, Carmen Capito, Slimane Allali, Narjis Yekkache, Michael Dussiot, Yann Nguyen, Agnès Lefort Des Ylouses, Béatrice Aussilhou, Magali Tichit, David Hardy, Blandine Maître, Anita Eckly, Mariane De Montalembert, Marina Cavazzana, Laure Joseph, Pierre Buffet, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mécanismes cellulaires et moléculaires des désordres hématologiques et implications thérapeutiques = Molecular mechanisms of hematological disorders and therapeutic implications (ERL 8254), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Neuropathologie expérimentale / Experimental neuropathology, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Biologie et Pharmacologie des Plaquettes sanguines : hémostase, thrombose, transfusion (BPP), Université de Strasbourg (UNISTRA)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), and ANR-20-CE17-0024,SpleenMark,Marqueurs de fonction splénique pour la pratique médicale(2020)
Subjects: Erythrocytes, [SDV]Life Sciences [q-bio], Vacuoles, Humans, Anemia, Sickle Cell, Hematology, Spleen, Fluorescent Dyes
Abstract: International audience
Published: 2022

170. New KCNN4 Variants Associated With Anemia: Stomatocytosis Without Erythrocyte Dehydration

Author: Allegrini, B., Jedele, S., Nguyen, L. David, Mignotet, M., Rapetti-Mauss, R., Etchebest, C., Fenneteau, O., Loubat, A., Boutet, A., Thomas, C., Durin, J., Petit, A., Badens, C., Garçon, Loïc, da Costa, Lydie, Guizouarn, H., Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité), Hôpital Robert Debré, Université Paris Cité (UPCité), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier de Saint-Nazaire, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, Rapetti-Mauss, Raphael, Bioinformatique génomique et moléculaire ((U 726)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Institute of Developmental Biology and Cancer (IBDC), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
Subjects: [SDV] Life Sciences [q-bio], Gardos, [SDV]Life Sciences [q-bio], Hereditary Xerocytosis, Stomatocytosis, red blood cell, KCNN4, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; The K + channel activated by the Ca 2+ , KCNN4, has been shown to contribute to red blood cell dehydration in the rare hereditary hemolytic anemia, the dehydrated hereditary stomatocytosis. We report two de novo mutations on KCNN4 , We reported two de novo mutations on KCNN4 , V222L and H340N, characterized at the molecular, cellular and clinical levels. Whereas both mutations were shown to increase the calcium sensitivity of the K + channel, leading to channel opening for lower calcium concentrations compared to WT KCNN4 channel, there was no obvious red blood cell dehydration in patients carrying one or the other mutation. The clinical phenotype was greatly different between carriers of the mutated gene ranging from severe anemia for one patient to a single episode of anemia for the other patient or no documented sign of anemia for the parents who also carried the mutation. These data compared to already published KCNN4 mutations question the role of KCNN4 gain-of-function mutations in hydration status and viability of red blood cells in bloodstream.
Published: 2022

171. Incidence of Acute Chest Syndrome in Children With Sickle Cell Disease Following Implementation of the 13-Valent Pneumococcal Conjugate Vaccine in France

Author: Zein Assad, Morgane Michel, Zaba Valtuille, Andrea Lazzati, Priscilla Boizeau, Fouad Madhi, Jean Gaschignard, Luu-Ly Pham, Marion Caseris, Robert Cohen, Florentia Kaguelidou, Emmanuelle Varon, Corinne Alberti, Albert Faye, François Angoulvant, Bérengère Koehl, Naïm Ouldali, Angoulvant, François, AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Caen Normandie (UNICAEN), Normandie Université (NU), Hôpital Hôtel-Dieu [Paris], Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Centre d'Investigation Clinique 1426 (CIC 1426), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHI Créteil, Groupe Hospitalier Nord Essonne [Longjumeau], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital Jean Verdier [AP-HP], Association Clinique et Thérapeutique Infantile du Val de Marne (ACTIV), Groupe d'Etude des Maladies Infectieuses Néonatales et Infantiles (GEMINI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-MRB-GRC, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire de Microbiologie Clinique [AP-HP Hôpital européen Georges-Pompidou], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), and Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité)
Subjects: Male, Vaccines, Conjugate, [SDV]Life Sciences [q-bio], Incidence, General Medicine, Anemia, Sickle Cell, [SDV] Life Sciences [q-bio], Cohort Studies, Streptococcus pneumoniae, Child, Preschool, Acute Chest Syndrome, Humans, Female, Child
Abstract: International audience; Importance: Acute chest syndrome (ACS) is one of the leading acute severe complications of sickle-cell disease (SCD). Although Streptococcus pneumoniae (S pneumoniae) is highly prevalent in children with SCD, its precise role in ACS is unclear. The efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) implementation on ACS is still unknown.Objective: To assess the association of PCV13 implementation in the general pediatric population with the incidence of ACS in children with SCD.Design, setting, and participants: This cohort study used an interrupted time-series analysis of patient records from a national hospital-based French surveillance system. All children younger than 18 years with SCD (based on the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision definition) hospitalized in France between January 2007 and December 2019 were included.Exposures: PCV13 implementation.Main outcomes and measures: Monthly incidence of ACS per 1000 children with SCD over time as analyzed by segmented linear regression with autoregressive error; monthly incidence of hospitalization for vaso-occlusive crisis, asthma crisis, and acute pyelonephritis per 1000 children with SCD over the same period as the control outcomes.Results: Among the 107 694 hospitalizations of children with SCD, 4007 episodes of ACS were included (median [IQR] age, 8 [4-12] years; 2228 [55.6%] boys). PCV13 implementation in 2010 was followed by a significant decrease in the incidence of ACS (-0.9% per month; 95% CI, -1.4% to -0.4%; P < .001), with an estimated cumulative change of -41.8% (95% CI, -70.8% to -12.7%) by 2019. Sensitivity analyses yielded the same results, including the incidence of ACS adjusted for that of vaso-occlusive crisis over time. The results were similar among different age groups. By contrast, no change was found for the 3 control outcomes over the study period.Conclusions and relevance: PCV13 implementation was associated with an important reduction in the incidence of ACS in children with SCD. This vaccine benefit provides new evidence of the key role of S pneumoniae in ACS and should be considered when estimating outcomes associated with current PCVs and the potential benefit of next-generation PCVs in children.
Published: 2022

172. β-Bulges: extensive structural analyses of β-sheets irregularities

Author: Craveur, Pierrick, Joseph, Agnel Praveen, Rebehmed, Joseph, De Brevern, Alexandre, GR-Ex, Laboratoire d'Excellence, GR-Ex, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Centre for Biological Sciences [TIFR] (NCBS), Tata Institute for Fundamental Research (TIFR), The Ministry of Research (France), The University Paris Diderot, Sorbonne Paris Cite (France), The National Institute of Blood Transfusion (INTS, France), The National Institute of Health and Medical Research (INSERM, France), The Laboratories of Excellence, GR-Ex (France), HFSP (India), NCBS (India), and de Brevern, Alexandre G.
Subjects: [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Protein Conformation, Molecular Sequence Data, Proteins, Hydrogen Bonding, Articles, bioinformatics, Molecular Dynamics Simulation, sequence, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Protein Structure, Secondary, protein aggregation, Evolution, Molecular, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, Amino Acids, protein structure, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], structure relationship, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract: International audience; β-Sheets are quite frequent in protein structures and are stabilized by regular main-chain hydrogen bond patterns. Irregularities in β-sheets, named β-bulges, are distorted regions between two consecutive hydrogen bonds. They disrupt the classical alternation of side chain direction and can alter the directionality of β-strands. They are implicated in protein-protein interactions and are introduced to avoid β-strand aggregation. Five different types of β-bulges are defined. Previous studies on β-bulges were performed on a limited number of protein structures or one specific family. These studies evoked a potential conservation during evolution. In this work, we analyze the β-bulge distribution and conservation in terms of local backbone conformations and amino acid composition. Our dataset consists of 66 times more β-bulges than the last systematic study (Chan et al. Protein Science 1993, 2:1574-1590). Novel amino acid preferences are underlined and local structure conformations are highlighted by the use of a structural alphabet. We observed that β-bulges are preferably localized at the N- and C-termini of β-strands, but contrary to the earlier studies, no significant conservation of β-bulges was observed among structural homologues. Displacement of β-bulges along the sequence was also investigated by Molecular Dynamics simulations.
Published: 2013

173. Genome-wide detection of sRNA targets with rNAV

Author: Patricia Thebault, Isabelle Dutour, Amine Ghozlane, Romain Bourqui, Jonathan Dubois, Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bourqui, Romain, Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)
Subjects: 0303 health sciences, business.industry, [INFO.INFO-DS]Computer Science [cs]/Data Structures and Algorithms [cs.DS], 030302 biochemistry & molecular biology, [INFO.INFO-DS] Computer Science [cs]/Data Structures and Algorithms [cs.DS], Genomics, Computational biology, Biology, Data science, Genome, Domain (software engineering), 03 medical and health sciences, Data visualization, Tree view, Transfer RNA, Functional activity, Area navigation, business, 030304 developmental biology
Abstract: International audience; The central dogma in molecular biology postulated that 'DNA makes RNA makes protein', however this dogma has been recently extended to integrate new biological activities involving small non- coding RNAs, called sRNAs. Accordingly, an increasing attention has been given to these molecules over the last decade and related experimental works have shown a wide range of functional activ- ities for these molecules. In this paper, we present rNAV (for rna NAVigator), a new tool for the visual exploration and analysis of sRNA-mediated regulatory networks. rNAV has been designed to help bioinformaticians and biologists to identify, from list of thou- sands of predictions, pertinent and reasonable sRNAs and target candidates for carrying out experimental validations. We propose a list of dedicated algorithms and interaction tools that facilitate the exploration of such networks. These algorithms can be gathered into pipelines which can then be saved and reuse over several sessions. To support exploration awareness, rNAV also provides an exploration tree view that allows to navigate through the steps of the analysis but also to select the -sub-networks to visualize and compare. These comparisons are facilitated by the integration of multiple and fully linked views. We demonstrate the usefulness of our approach by a case study on Escherichia coli bacteria performed by domain experts.
Published: 2013

174. Structural Model of the Anion Exchanger 1 (SLC4A1) and Identification of Transmembrane Segments Forming the Transport Site

Author: Hélène Guizouarn, Catherine Etchebest, Damien Barneaud-Rocca, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS)
Subjects: Anions, Models, Molecular, Bicarbonate, Inorganic chemistry, Molecular Sequence Data, Bicarbonate transporter protein, Lithium, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, Xenopus laevis, Protein structure, stomatognathic system, Membrane Biology, Anion Exchange Protein 1, Erythrocyte, Animals, Humans, Point Mutation, Homology modeling, Amino Acid Sequence, Sulfhydryl Compounds, Molecular Biology, Band 3, Ion channel, 030304 developmental biology, 0303 health sciences, Binding Sites, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], 030302 biochemistry & molecular biology, Cell Membrane, Sodium, Cell Biology, Transmembrane protein, Protein Structure, Tertiary, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], stomatognathic diseases, chemistry, Symporter, biology.protein, Biophysics, Mutagenesis, Site-Directed, Oocytes, Potassium, Female
Abstract: The anion exchanger 1 (AE1), a member of bicarbonate transporter family SLC4, mediates an electroneutral chloride/bicarbonate exchange in physiological conditions. However, some point mutations in AE1 membrane-spanning domain convert the electroneutral anion exchanger into a Na+ and K+ conductance or induce a cation leak in a still functional anion exchanger. The molecular determinants that govern ion movement through this transporter are still unknown. The present study was intended to identify the ion translocation pathway within AE1. In the absence of a resolutive three-dimensional structure of AE1 membrane-spanning domain, in silico modeling combined with site-directed mutagenesis experiments was done. A structural model of AE1 membrane-spanning domain is proposed, and this model is based on the structure of a uracil-proton symporter. This model was used to design cysteine-scanning mutagenesis on transmembrane (TM) segments 3 and 5. By measuring AE1 anion exchange activity or cation leak, it is proposed that there is a unique transport site comprising TM3–5 and TM8 that should function as an anion exchanger and a cation leak. Background: There is still no high resolution three-dimensional structure available for the membrane-spanning domain of anion exchanger 1 (AE1). Results: A three-dimensional model of AE1 membrane-spanning domain has been generated in silico and experimentally assessed. Conclusion: Transmembrane segments forming AE1 transport site have been identified. Significance: This is the first three-dimensional model of AE1 membrane-spanning domain based on a cation symporter.
Published: 2013

175. Evolution study of the Baeyer-Villiger monooxygenases enzyme family: functional importance of the highly conserved residues

Author: Véronique de Berardinis, Véronique Alphand, Alexandre G. de Brevern, Joseph Rebehmed, GR-Ex, Laboratoire d'Excellence, GR-Ex, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), The Ministry of Research (France) The University Paris Diderot, Sorbonne Paris Cite (France) The National Institute of Blood Transfusion (INTS, France) The National Institute of Health and Medical Research (INSERM, France) The Laboratories of Excellence, GR-Ex (France) The National Center for Atomic Research (CEA,France) University d'Aix-Marseille (France) The National Center for Scientific Research (CNRS,France) high performance computing (HPC) resources at the French National Computing Center CINES under grant no. 2012-c2012076930 funded by the GENCI (Grand Equipement National de Calcul Intensif)., Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Génomique métabolique (UMR 8030), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), and de Brevern, Alexandre G.
Subjects: Threonine, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, ketones, phylogeny, 01 natural sciences, Biochemistry, Conserved sequence, Mixed Function Oxygenases, Protein structure, esters, Rhodococcus, [INFO.INFO-BT]Computer Science [cs]/Biotechnology, lactones, Conserved Sequence, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], chemistry.chemical_classification, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [CHIM.ORGA]Chemical Sciences/Organic chemistry, enentioselectivity, [CHIM.CATA] Chemical Sciences/Catalysis, General Medicine, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Amino acid, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, [SDV.TOX] Life Sciences [q-bio]/Toxicology, [SDV.TOX]Life Sciences [q-bio]/Toxicology, sequence alignment, Flavin-Adenine Dinucleotide, Stereochemistry, Sequence alignment, Biology, 010402 general chemistry, stereoselectivity, 03 medical and health sciences, Pseudomonas, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, protein structure, 030304 developmental biology, function, Binding Sites, [CHIM.CATA]Chemical Sciences/Catalysis, Monooxygenase, interactions, [CHIM.ORGA] Chemical Sciences/Organic chemistry, 0104 chemical sciences, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, Enzyme binding, [INFO.INFO-BT] Computer Science [cs]/Biotechnology, chemistry, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Function (biology), NADP
Abstract: International audience; Baeyer-Villiger monooxygenases (BVMOs) catalyze the transformation of linear and cyclic ketones into their corresponding esters and lactones by introducing an oxygen atom into a C-C bond. This bioreaction has numerous advantages compared to its chemical version; it does not induce the use of potentially harmful reagents (i.e., green chemistry) and displays significant better enantio- and regio-selectivity. New potential BVMOs were searched using sequence homology for type I BVMO proteins. 116 new sequences were identified as new putative BVMOs respecting the defined selection criteria. Multiple sequence alignments were carried out on the selected sequences to study the conservation of structurally and/or functionally important amino acids during evolution. Type I BVMO signature motif was found to be conserved in 94.8% of the sequences. We noticed also the highly conserved - but previously unnoticed - Threonine 167 (93.1%), located in the signature motif; this position could be added in the pattern used to characterize specific Type I enzymes. Amino acids at the vicinity of the FAD and NADPH cofactors were found also to be highly conserved and the details of the interactions were emphasized. Interestingly, residues at the enzyme binding site were found less conserved in terms of sequence evolution, leading sometimes to some important amino acid changes. These behaviors could explain the enzyme selectivity and specificity for different ligands.
Published: 2013

176. VLDP web server: a powerful geometric tool for analysing protein structures in their environment

Author: Alexandre G. de Brevern, Jeremy Esque, Sylvain Leonard, Christophe Oguey, Laboratoire de Physique Théorique et Modélisation (LPTM - UMR 8089), Centre National de la Recherche Scientifique (CNRS)-CY Cergy Paris Université (CY), GR-Ex, Laboratoire d'Excellence, GR-Ex, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Ministry of Research (France) The University Paris Diderot, Sorbonne Paris Cite (France) The National Institute of Blood Transfusion (INTS, France) The National Institute of Health and Medical Research (INSERM, France) The Laboratories of Excellence, GR-Ex (France) The University of Cergy-Pontoise (France) The National Center for Scientific Research (CNRS,France), de Brevern, Alexandre G., and Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)
Subjects: Models, Molecular, Web server, MESH: Amino Acids, Protein Conformation, Voronoi, protein accessibility, Biology, Bioinformatics, computer.software_genre, 01 natural sciences, tessellations, Set (abstract data type), 03 medical and health sciences, MESH: Software, Protein structure, MESH: Protein Conformation, 0103 physical sciences, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetics, MESH: Proteins, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], 030304 developmental biology, Delaunay, Internet, 0303 health sciences, amino acids, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Tessellation, 010304 chemical physics, Delaunay triangulation, Proteins, Articles, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Visualization, MESH: Internet, protein structures, Laguerre polynomials, protein volume, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Voronoi diagram, computer, Algorithm, Software, MESH: Models, Molecular
Abstract: International audience; Protein structures are an ensemble of atoms determined experimentally mostly by X-ray crystallography or Nuclear Magnetic Resonance. Studying 3D protein structures is a key point for better understanding protein function at a molecular level. We propose a set of accurate tools, for analysing protein structures, based on the reliable method of Voronoi-Laguerre tessellations. The Voronoi Laguerre Delaunay Protein web server (VLDPws) computes the Laguerre tessellation on a whole given system first embedded in solvent. Through this fine description, VLDPws gives the following data: (i) Amino acid volumes evaluated with high precision, as confirmed by good correlations with experimental data. (ii) A novel definition of inter-residue contacts within the given protein. (iii) A measure of the residue exposure to solvent that significantly improves the standard notion of accessibility in some cases. At present, no equivalent web server is available. VLDPws provides output in two complementary forms: direct visualization of the Laguerre tessellation, mostly its polygonal molecular surfaces; files of volumes; and areas, contacts and similar data for each residue and each atom. These files are available for download for further analysis. VLDPws can be accessed at http://www.dsimb.inserm.fr/dsimb_tools/vldp.
Published: 2013

177. A new method for spectral characterization of protein families from sequence information using Fourier Transform

Author: Berland, Magali, Offmann, Bernard, André, Isabelle, Remaud Simeon, Magali, Charton, Philippe, Unité de fonctionnalité et ingénierie de protéines (UFIP), Université de Nantes - Faculté des Sciences et des Techniques, Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS), Laboratoire d'Informatique et de Mathématiques (LIM), Université de La Réunion (UR), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [INFO]Computer Science [cs], ComputingMilieux_MISCELLANEOUS
Abstract: C-AFFC-AFF; International audience; no abstract
Published: 2013

178. PRR repeats in the intracellular domain of KISS1R are important for its export to cell membrane

Author: Chevrier, Lucie, De Brevern, Alexandre, Hernandez, Eva, Leprince, Jérome, Vaudry, Hubert, Guedj, Anne Marie, De Roux, Nicolas, Physiopathologie et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), GR-Ex, Laboratoire d'Excellence, GR-Ex, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Maladies Métaboliques et Endocriniennes, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), INSERM UMR676, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Laboratoire de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, and de Brevern, Alexandre G.
Subjects: DNA Mutational Analysis, Gene Expression, MESH: Receptors, G-Protein-Coupled, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH: Base Sequence, MESH: Hypogonadism, Receptors, MESH: Obesity, MESH: Animals, MESH: Molecular Dynamics Simulation, MESH: Proline-Rich Protein Domains, MESH: DNA Mutational Analysis, MESH: Genetic Association Studies, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, variants, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH: COS Cells, Protein Transport, MESH: HEK293 Cells, Proline-Rich Protein Domains, structural alphabet, MESH: Protein Transport, MESH: Gene Expression, Molecular Sequence Data, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Molecular Dynamics Simulation, G-Protein-Coupled, male, Insertional, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, protein structure, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, MESH: Adolescent, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, MESH: Molecular Sequence Data, Hypogonadism, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, MESH: Cercopithecus aethiops, MESH: Male, MESH: Mutagenesis, Insertional, Mutagenesis, adolescent, MESH: HeLa Cells, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Cell Membrane
Abstract: The National Institute of Health and Medical Research (INSERM, France) The Ministry of Research (France) The University Paris Diderot, Sorbonne Paris Cite (France) The National Institute of Blood Transfusion (INTS, France) The Laboratories of Excellence, GR-Ex (France); International audience; Inactivating mutations of KISS-1 receptor (KISS1R) have been recently described as a rare cause of isolated hypogonadotropic hypogonadism transmitted as a recessive trait. Few mutations have been described, and the structure-function relationship of KISS1R remains poorly understood. Here, we have taken advantage of the discovery of a novel mutation of KISS1R to characterize the structure and function of an uncommon protein motif composed of 3 proline-arginine-arginine (PRR) repeats located within the intracellular domain. A heterozygous insertion of 1 PRR repeat in-frame with 3 PRR repeats leading to synthesis of a receptor bearing 4 PRR repeats (PRR-KISS1R) was found in the index case. Functional analysis of PRR-KISS1R showed a decrease of the maximal response to kisspeptin stimulation, associated to a lower cell surface expression without modification of total expression. PRR-KISS1R exerts a dominant negative effect on the synthesis of the wild-type (WT)-KISS1R. This effect was due to the nature of inserted residues but also to the difference of the length of the intracellular domain between PRR-KISS1R and WT-KISS1R. A molecular dynamic analysis showed that the additional PRR constrained this arginine-rich region into a polyproline type II helix. Altogether, this study shows that a heterozygous insertion in KISS1R may lead to hypogonadotropic hypogonadism by a dominant negative effect on the WT receptor. An additional PRR repeat into a proline-arginine-rich motif can dramatically changed the conformation of the intracellular domain of KISS1R and its probable interaction with partner proteins.
Published: 2013

179. PRR repeats in the intracellular domain of KISS1R are important for its export to cell membrane.: PRR repeats in intracellular domain of KISSIR

Author: Anne Marie Guedj, Lucie Chevrier, Nicolas de Roux, Alexandre G. de Brevern, Jérôme Leprince, Eva Hernandez, Hubert Vaudry, Physiopathologie et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), GR-Ex, Laboratoire d'Excellence, GR-Ex, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Maladies Métaboliques et Endocriniennes, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), INSERM UMR676, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Laboratoire de Biochimie, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré
Subjects: DNA Mutational Analysis, Gene Expression, MESH: Receptors, G-Protein-Coupled, MESH: Base Sequence, MESH: Hypogonadism, Receptors, G-Protein-Coupled, 0302 clinical medicine, Endocrinology, Protein structure, Chlorocebus aethiops, Receptors, MESH: Obesity, MESH: Animals, MESH: Molecular Dynamics Simulation, MESH: Proline-Rich Protein Domains, MESH: DNA Mutational Analysis, Structural motif, Original Research, MESH: Genetic Association Studies, Genetics, 0303 health sciences, variants, COS cells, General Medicine, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Transport protein, Cell biology, MESH: COS Cells, Protein Transport, 030220 oncology & carcinogenesis, MESH: HEK293 Cells, COS Cells, Proline-Rich Protein Domains, structural alphabet, Isolated hypogonadotropic hypogonadism, MESH: Protein Transport, MESH: Gene Expression, Molecular Sequence Data, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Molecular Dynamics Simulation, 03 medical and health sciences, G-Protein-Coupled, male, Insertional, medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Obesity, protein structure, Molecular Biology, Genetic Association Studies, 030304 developmental biology, Polyproline helix, MESH: Adolescent, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, Hypogonadism, Cell Membrane, HEK 293 cells, Heterozygote advantage, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, medicine.disease, MESH: Cercopithecus aethiops, MESH: Male, Mutagenesis, Insertional, HEK293 Cells, MESH: Mutagenesis, Insertional, Mutagenesis, adolescent, MESH: HeLa Cells, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], HeLa Cells, Receptors, Kisspeptin-1, MESH: Cell Membrane
Abstract: The National Institute of Health and Medical Research (INSERM, France) The Ministry of Research (France) The University Paris Diderot, Sorbonne Paris Cite (France) The National Institute of Blood Transfusion (INTS, France) The Laboratories of Excellence, GR-Ex (France); International audience; Inactivating mutations of KISS-1 receptor (KISS1R) have been recently described as a rare cause of isolated hypogonadotropic hypogonadism transmitted as a recessive trait. Few mutations have been described, and the structure-function relationship of KISS1R remains poorly understood. Here, we have taken advantage of the discovery of a novel mutation of KISS1R to characterize the structure and function of an uncommon protein motif composed of 3 proline-arginine-arginine (PRR) repeats located within the intracellular domain. A heterozygous insertion of 1 PRR repeat in-frame with 3 PRR repeats leading to synthesis of a receptor bearing 4 PRR repeats (PRR-KISS1R) was found in the index case. Functional analysis of PRR-KISS1R showed a decrease of the maximal response to kisspeptin stimulation, associated to a lower cell surface expression without modification of total expression. PRR-KISS1R exerts a dominant negative effect on the synthesis of the wild-type (WT)-KISS1R. This effect was due to the nature of inserted residues but also to the difference of the length of the intracellular domain between PRR-KISS1R and WT-KISS1R. A molecular dynamic analysis showed that the additional PRR constrained this arginine-rich region into a polyproline type II helix. Altogether, this study shows that a heterozygous insertion in KISS1R may lead to hypogonadotropic hypogonadism by a dominant negative effect on the WT receptor. An additional PRR repeat into a proline-arginine-rich motif can dramatically changed the conformation of the intracellular domain of KISS1R and its probable interaction with partner proteins.
Published: 2013

180. Classification des journées en fonction des radiations solaires sur l'île de la Réunion

Author: Bessafi, Miloud, De Carvahlo, Francisco De A.T., Charton, Philippe, Delsaut, Mathieu, Despeyroux, Thierry, Jeanty, Patrick, Lan Sun Luk, Jean-Daniel, Lechevallier, Yves, Ralambondrainy, Henri, Trovalet, Lionel, Laboratoire d'Energétique, d'Electronique et Procédés (LE2P), Université de La Réunion (UR), Centro de Informatica UFPE [Recife] (CIn), Universidade Federal de Pernambuco [Recife] (UFPE), Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS), Usage-centered design, analysis and improvement of information systems (AxIS), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique (Inria), Laboratoire d'Informatique et de Mathématiques (LIM), SfDS, Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Energy Lab (ENERGY Lab), and Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)
Subjects: Classification automatique, [STAT.ML]Statistics [stat]/Machine Learning [stat.ML], analyse de courbes
Abstract: National audience; L'objectif de cet article est de montrer les intérêts et les inconvénients de deux approches classificatoires de courbes. La première est basée sur une représentation des courbes sous forme vectorielle, la seconde propose la distance de D'Urso et Vichi qui est basée sur les première et seconde dérivées finies. Cette dernière intègre au mieux les propriétés mathématiques des courbes. Ces deux approches seront appliquées à la classification de sources de production d'énergie de type photovoltaïque.
Published: 2013

181. Cis-trans isomerization of omega dihedrals in proteins

Author: Pierrick Craveur, Pierre Poulain, Joseph Rebehmed, Agnel Praveen Joseph, Alexandre G. de Brevern, de Brevern, Alexandre G., GR-Ex, Laboratoire d'Excellence, GR-Ex, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), National Centre for Biological Sciences [TIFR] (NCBS), Tata Institute for Fundamental Research (TIFR), The Ministry of Research (France) The University Paris Diderot, Sorbonne Paris Cite (France) The National Institute of Blood Transfusion (INTS, France) The National Institute of Health and Medical Research (INSERM, France) The Laboratories of Excellence, GR-Ex (France) HFSP (India), and Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Models, Molecular, cis-trans-Isomerases, Protein Folding, Stereochemistry, Protein Conformation, MESH: Protein Folding, Clinical Biochemistry, Dihedral angle, Molecular Dynamics Simulation, 010402 general chemistry, Crystallography, X-Ray, 01 natural sciences, Biochemistry, iPBA, 03 medical and health sciences, Molecular dynamics, Protein structure, MESH: Protein Conformation, MESH: Protein Stability, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Peptide bond, Humans, MESH: Molecular Dynamics Simulation, MESH: Proteins, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, protein superimposition, 030304 developmental biology, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH: Humans, Chemistry, Protein Stability, Organic Chemistry, Proteins, Protein structure prediction, protein function, MESH: Crystallography, X-Ray, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Cis trans isomerization, 0104 chemical sciences, protein structures, Protein folding, structural alphabet, isomerisation, MESH: cis-trans-Isomerases, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Isomerization, MESH: Models, Molecular
Abstract: International audience; Peptide bonds in protein structures are mainly found in trans conformation with a torsion angle ω close to 180°. Only a very low proportion is observed in cis conformation with ω angle around 0°. Cis-trans isomerization leads to local conformation changes which play an important role in many biological processes. In this paper, we reviewed the recent discoveries and research achievements in this field. First, we presented some interesting cases of biological processes in which cis-trans isomerization is directly implicated. It is involved in protein folding and various aspect of protein function like dimerization interfaces, autoinhibition control, channel gating, membrane binding. Then we reviewed conservation studies of cis peptide bonds which emphasized evolution constraints in term of sequence and local conformation. Finally we made an overview of the numerous molecular dynamics studies and prediction methodologies already developed to take into account this structural feature in the research area of protein modeling. Many cis peptide bonds have not been recognized as such due to the limited resolution of the data and to the refinement protocol used. Cis-trans proline isomerization reactions represents a vast and promising research area that still needs to be further explored for a better understanding of isomerization mechanism and improvement of cis peptide bond predictions.
Published: 2013

182. JAK2V617F activates Lu/BCAM-mediated red cell adhesion in polycythemia vera through an EpoR-independent Rap1/Akt pathway

Author: De Grandis, Maria, Cambot, Marie, Wautier, Marie-Paule, Cassinat, Bruno, Chomienne, Christine, Colin, Yves, Wautier, Jean-Luc, Le Van Kim, Caroline, El Nemer, Wassim, Protéines de la membrane érythrocytaire et homologues non-érythroides, Université des Antilles et de la Guyane (UAG)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), GR-Ex, Laboratoire d'Excellence, Institut National de la Transfusion Sanguine [Paris] (INTS), Unite de Biologie Cellulaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hématologie -Immunologie -Cibles thérapeutiques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), The work was funded by the Institut National de la Santé et de la Recherche Médicale (Inserm), the Institut National de la Transfusion Sanguine (INTS), and a grant from Région Île-de-France (SESAME 2007 no. F-08-1104/R). The PhD student, Maria De Grandis, was funded by the Ministère de l'Enseignement Supérieur et de la Recherche at the Ecole Doctorale B3MI., and El Nemer, Wassim
Subjects: MESH: Aged, MESH: Signal Transduction, MESH: Middle Aged, MESH: rap1 GTP-Binding Proteins, MESH: Humans, MESH: Phosphorylation, MESH: Proto-Oncogene Proteins c-akt, MESH: Erythrocytes, MESH: Laminin, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, MESH: Polycythemia Vera, MESH: Male, MESH: Janus Kinase 2, MESH: Cell Adhesion, MESH: Cell Line, MESH: Aged, 80 and over, MESH: Lutheran Blood-Group System, MESH: Cell Adhesion Molecules, MESH: Animals, MESH: Receptors, Erythropoietin, MESH: Mice, MESH: Female, [SDV.BC] Life Sciences [q-bio]/Cellular Biology
Abstract: International audience; Polycythemia vera (PV) is characterized by an increased RBC mass, spontaneous erythroid colony formation, and the JAK2V617F mutation. PV is associated with a high risk of mesenteric and cerebral thrombosis. PV RBC adhesion to endothelial laminin is increased and mediated by phosphorylated erythroid Lu/BCAM. In the present work, we investigated the mechanism responsible for Lu/BCAM phosphorylation in the presence of JAK2V617F using HEL and BaF3 cell lines as well as RBCs from patients with PV. High levels of Rap1-GTP were found in HEL and BaF3 cells expressing JAK2V617F compared with BaF3 cells with wild-type JAK2. This finding was associated with increased Akt activity, Lu/BCAM phosphorylation, and cell adhesion to laminin that were inhibited by the dominant-negative Rap1S17N or by the specific Rap1 inhibitor GGTI-298. Surprisingly, knocking-down EpoR in HEL cells did not alter Akt activity or cell adhesion to laminin. Our findings reveal a novel EpoR-independent Rap1/Akt signaling pathway that is activated by JAK2V617F in circulating PV RBCs and responsible for Lu/BCAM activation. This new characteristic of JAK2V617F could play a critical role in initiating abnormal interactions among circulating and endothelial cells in patients with PV.
Published: 2013

183. Impact of hepatitis B and delta virus co-infection on liver disease in Mauritania: a cross sectional study

Author: Mohamed Aye, Ségolène Brichler, Abdellahi Ould Amar, Françoise Lunel-Fabiani, Michel Rosenheim, F Zahra Fall Malick, Alexandra Ducancelle, Emmanuel Gordien, Pascal Veillon, Frédéric Le Gal, Wael Y. Mansour, Lô Baïdy, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre national de référence des virus des hépatites B, C et Delta, Université Paris 13 (UP13)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe hospitalier Henri-Mondor, Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Groupe hospitalier Henri-Mondor
Subjects: Microbiology (medical), Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, FIBROMETER, Adolescent, Cross-sectional study, viruses, [SDV]Life Sciences [q-bio], medicine.disease_cause, Gastroenterology, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Risk Factors, Internal medicine, Medicine, Humans, Hepatitis Antibodies, hepatitis Delta virus, 030304 developmental biology, Aged, Hepatitis B virus, 0303 health sciences, Analysis of Variance, business.industry, Coinfection, Mauritania, virus diseases, Hepatitis B, Middle Aged, medicine.disease, Hepatitis D, 3. Good health, Infectious Diseases, Cross-Sectional Studies, Immunology, 030211 gastroenterology & hepatology, Female, business, hepatitis B virus
Abstract: International audience; OBJECTIVES: Mauritania is a highly endemic region for hepatitis B (HBV) and delta (HDV) viruses. No data are available on HDV's impact on the severity of liver disease in consecutive HBV-infected patients in Africa. This study evaluated the degree of liver fibrosis in a cohort of chronic HBV carriers.METHODS: Three-hundred consecutive HBV-infected Mauritanian patients were checked for HDV infection via the detection of anti-HDV antibodies (Ab) and viral RNA. HBV- vs. HBV/HDV-infected patients were compared by physical examination, biological analyses, and the APRI (aspartate aminotransferase to platelet ratio index) and FibroMeter tests for determination of liver fibrosis.RESULTS: More than 30% of the patients had anti-HDVAb. Among these, 62.2% were HDV-RNA positive. Co-infected patients were older (>8-years) than HBV-mono-infected patients. They had more liver tests abnormalities and clinical or ultrasound signs of liver fibrosis. APRI and FibroMeter scores were also significantly increased in these patients. In multivariate analysis, beyond HDVAb, male gender and HBV-VL >3.7logIU/mL were the only markers linked to significant liver fibrosis.CONCLUSIONS: In Mauritania, HDV co-infection worsens liver disease, both clinically and biologically, as confirmed by the APRI and FibroMeter tests. These tests may be useful for the management of delta hepatitis, which is a major health problem in Mauritania.
Published: 2013

184. Mice Expressing RHAG and RHD Human Blood Group Genes

Author: Ulrich Cortes, Jean-Pierre Cartron, Isabelle Mouro-Chanteloup, Sylvain Métral, Isabelle Callebaut, Julien Picot, Dominique Goossens, Nelly da Silva, Institut National de la Transfusion Sanguine [Paris] (INTS), Inserm UMR_S 665, Institut National de la Santé et de la Recherche Médicale (INSERM), Protéines de la membrane érythrocytaire et homologues non-érythroides, Université des Antilles et de la Guyane (UAG)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de minéralogie et de physique des milieux condensés (IMPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Institut de Physique du Globe de Paris (IPG Paris)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Transfusion Sanguine, Paris, France, Inserm UMR_S 665, Paris, France, Université Paris Diderot, Sorbonne Paris Cité, UMR-S665, Paris, France, Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de recherche pour le développement [IRD] : UR206-Centre National de la Recherche Scientifique (CNRS), and Mouro-Chanteloup, Isabelle
Subjects: Genetically modified mouse, Male, Erythrocytes, Transcription, Genetic, Transgene, [SDV]Life Sciences [q-bio], lcsh:Medicine, Gene Expression, Mice, Transgenic, beta-Globins, Biology, Cell Line, 03 medical and health sciences, Mice, 0302 clinical medicine, Gene expression, Ammonium Compounds, Animals, Humans, lcsh:Science, Promoter Regions, Genetic, Gene, Cation Transport Proteins, 030304 developmental biology, Regulation of gene expression, Mice, Knockout, 0303 health sciences, Multidisciplinary, Membrane Glycoproteins, Rh-Hr Blood-Group System, lcsh:R, Erythrocyte Membrane, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Blood Proteins, Molecular biology, [SDV] Life Sciences [q-bio], Membrane glycoproteins, Gene Expression Regulation, Knockout mouse, RHAG, biology.protein, lcsh:Q, Protein Multimerization, 030215 immunology, Protein Binding, Research Article
Abstract: International audience; Anti-RhD prophylaxis of haemolytic disease of the fetus and newborn (HDFN) is highly effective, but as the suppressive mechanism remains uncertain, a mouse model would be of interest. Here we have generated transgenic mice expressing human RhAG and RhD erythrocyte membrane proteins in the presence and, for human RhAG, in the absence, of mouse Rhag. Human RhAG associates with mouse Rh but not mouse Rhag on red blood cells. In Rhag knockout mice transgenic for human RHAG, the mouse Rh protein is " rescued " (re-expressed), and co-immunoprecipitates with human RhAG, indicating the presence of hetero-complexes which associate mouse and human proteins. RhD antigen was expressed from a human RHD gene on a BAC or from RHD cDNA under control of β-globin regulatory elements. RhD was never observed alone, strongly indicative that its expression absolutely depends on the presence of transgenic human RhAG. This first expression of RhD in mice is an important step in the creation of a mouse model of RhD allo-immunisation and HDFN, in conjunction with the Rh-Rhag knockout mice we have developed previously.
Published: 2013

185. DoSA: Database of Structural Alignments

Author: Alexandre G. de Brevern, Bernard Offmann, Garima Agarwal, Narayanaswamy Srinivasan, Mohammed Iftekhar, Swapnil Mahajan, Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Molecular Biophysics Unit, Indian Institute of Science, GR-Ex, Laboratoire d'Excellence, GR-Ex, National Centre for Biological Sciences [TIFR] (NCBS), Tata Institute for Fundamental Research (TIFR), Unité de fonctionnalité et ingénierie de protéines (UFIP), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), MBU, Indian Institute of Science-Indian Institute of Science, Indo-French collaborative grant (CEFIPRA/IFCPAR 3903-E) The Ministry of Research (France) The University Paris Diderot, Sorbonne Paris Cite (France) The National Institute of Blood Transfusion (INTS, France) The National Institute of Health and Medical Research (INSERM, France) The Laboratories of Excellence, GR-Ex (France) The University of Nantes (France) Fonds Européen de Dévelopment Régional and Conseil Regional de La Réunion [20100079, Tiers: 144645] Department of Biotechnology (India), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), and de Brevern, Alexandre G.
Subjects: Models, Molecular, PALI, substitution matrix, optimisation, Statistics as Topic, MESH: Amino Acid Sequence, Molecular Biophysics Unit, computer.software_genre, Protein structure, MESH: Proteins, Databases, Protein, Structural motif, database, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Structural Homology, Protein, 0303 health sciences, Protein function, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Database, 030302 biochemistry & molecular biology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], CLUSTALW, Original Article, Structural alphabet, General Agricultural and Biological Sciences, MESH: Models, Molecular, Information Systems, MESH: Databases, Protein, Molecular Sequence Data, Biology, iPBA, General Biochemistry, Genetics and Molecular Biology, Substitution matrix, Access to Information, 03 medical and health sciences, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, protein structure, Spatial Orientations, MESH: Statistics as Topic, 030304 developmental biology, MESH: Molecular Sequence Data, Proteins, Protein superfamily, MESH: Access to Information, Functional integrity, Structural Homology, Protein, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], protein structure superimposition, computer
Abstract: International audience; Protein structure alignment is a crucial step in protein structure-function analysis. Despite the advances in protein structure alignment algorithms, some of the local conformationally similar regions are mislabeled as structurally variable regions (SVRs). These regions are not well superimposed because of differences in their spatial orientations. The Database of Structural Alignments (DoSA) addresses this gap in identification of local structural similarities obscured in global protein structural alignments by realigning SVRs using an algorithm based on protein blocks. A set of protein blocks is a structural alphabet that abstracts protein structures into 16 unique local structural motifs. DoSA provides unique information about 159,780 conformationally similar and 56,140 conformationally dissimilar SVRs in 74 705 pairwise structural alignments of homologous proteins. The information provided on conformationally similar and dissimilar SVRs can be helpful to model loop regions. It is also conceivable that conformationally similar SVRs with conserved residues could potentially contribute toward functional integrity of homologues, and hence identifying such SVRs could be helpful in understanding the structural basis of protein function. Database URL: http://bo-protscience.fr/dosa/
Published: 2013

186. Hemorheological alterations, decreased cerebral microvascular oxygenation and cerebral vasomotion compensation in sickle cell patients

Author: Waltz, Xavier, Pichon, Aurélien, Mougenel, Danièle, Lemonne, Nathalie, Lalanne-Mistrih, Marie-Laure, Sinnapah, Stéphane, Tarer, Vanessa, Tressières, Benoit, Lamarre, Yann, Etienne-Julan, Maryse, Hue, Olivier, Hardy-Dessources, Marie-Dominique, Connes, Philippe, Adaptations au Climat Tropical, Exercice et Santé (ACTES), Université des Antilles et de la Guyane (UAG), Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Réponses Cellulaires et Fonctionnelles à l'Hypoxie (LRPH), Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-UFR SMBH, Unité Transversale de la Drépanocytose, CHU Pointe-à-Pitre/Abymes [Guadeloupe], Centre d'investigation clinique Antilles-Guyane (CIC - Antilles Guyane), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU de la Martinique [Fort de France]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Service d'Orthopédie et de Traumatologie, Université des Antilles et de la Guyane (UAG)-CHU Pointe-à-Pitre/Abymes [Guadeloupe], This work was supported by local grants from the Academic Hospital of Pointe-à-Pitre (PHRC CHU de Pointe à Pitre). PhD funding of X.W. was supported by the association 'Ensemble contre la drépanocytose' and by the regional council of Guadeloupe, and CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles et de la Guyane (UAG)
Subjects: MESH: Humans, hypoxia, brain, microcirculation, MESH: Adult, MESH: Cerebrovascular Circulation, MESH: Hemoglobin SC Disease, MESH: Hemorheology, MESH: Male, MESH: Brain, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Oxygen Consumption, MESH: Brain Chemistry, Hemoglobinopathy, oxygen, MESH: Female, MESH: Oxygen
Abstract: International audience; Sickle cell anemia (SS) is characterized by a reduced cerebral microvascular oxygen saturation (cerebral TOI), which is not associated with hemoglobin concentration. Cerebral TOI has never been studied in sickle cell-hemoglobin C disease (SC). We focused on the relationships between hemorheological alterations and cerebral TOI in sickle cell patients with no cerebral vasculopathy and on the usefulness of TOI variability to assess the cerebral vasomotion activity. The blood rheological profile, the level of cerebral TOI (spatial resolved spectroscopy) and the cerebral TOI variability, which reflects vasomotion activity, were compared between 20 healthy subjects (AA), 21 SC patients, and 21 SS patients. Cerebral TOI exhibited the following order: AA > SC > SS. The low cerebral TOI in SS patients was related to red blood cell aggregation and deformability properties. The cerebral TOI variability of SS and SC patients was increased above healthy values and vasomotion activity was negatively associated with the reduced cerebral TOI in SS patients. We demonstrated that (1) blood rheology could be involved in the reduced cerebral TOI in SS patients but not in SC patients; (2) vasomotion activity is increased in SS and SC patients to compensate for the reduced cerebral TOI.
Published: 2012

187. Challenges in transfusion-transmitted infection screening in Sub-Saharan Africa

Author: Daniel Candotti, Claude Tagny-Tayou, Syria Laperche, Institut National de la Transfusion Sanguine [Paris] (INTS), University of Yaoundé [Cameroun], and Candotti, Daniel
Subjects: Nucleic acid testing, medicine.medical_specialty, Sub saharan, Quality management, media_common.quotation_subject, Clinical Biochemistry, Blood Donors, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Economic assessment, medicine, Humans, Blood Transfusion, Transfusion-transmission, Transfusion transmitted infection, Quality (business), Intensive care medicine, Africa South of the Sahara, media_common, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Sub-Saharan Africa, Biochemistry (medical), Blood Screening, Transfusion Reaction, Hematology, 3. Good health, Serology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Sustainability, Blood safety, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Business, 030215 immunology
Abstract: International audience; In Sub-Saharan Africa, high clinical demand for transfusion faces endemic bloodborne infections and limited resources. Blood screening for transfusion-transmitted bloodborne pathogens is the cornerstone of blood safety. Although there have been substantial improvements over the years, challenges in transfusion-transmitted infection screening that have been identified repeatedly long ago still need to be addressed. Affordability and sustainability of state-of-the-art quality assessed serological and molecular assays, and associated confirmation strategies remain of real concern. In addition, limited resources and infrastructures hamper the development of adequate facilities, quality management, and staff qualification, and exacerbate shortage of reagents and equipment maintenance. It is also important to maintain effort in constituting pools of repeat voluntary non-remunerated donors. Alternative strategies for blood screening that take into account local circumstances might be desirable but they should rely on appropriate field evaluation and careful economic assessment rather than dogma established from high-resource settings.
Published: 2021

188. Progressive structure-based alignment of homologous proteins: Adopting sequence comparison strategies

Author: Joseph, Agnel Praveen, Srinivasan, Narayanaswamy, De Brevern, Alexandre, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Molecular Biophysics Unit, Indian Institute of Science, French Ministry of Research, University of Paris Diderot - Paris 7, Sorbone Paris Cité, French National Institute for Blood Transfusion (INTS), French Institute for Health and Medical Research (INSERM), Indian Department of Biotechnology, CEFIPRA/IFCPAR for collaborative grant (number 3903-E)., and de Brevern, Alexandre G.
Subjects: [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], MESH: Sequence Homology, Amino Acid, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], MESH: Sequence Alignment, structure conservation, protein structure mining, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH: Protein Conformation, Protein Data Bank, Protein Blocks, anchor-based alignment, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, structural alphabet, MESH: Proteins, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, protein structure comparison, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Models, Molecular, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract: International audience; Comparison of multiple protein structures has a broad range of applications in the analysis of protein structure, function and evolution. Multiple structure alignment tools (MSTAs) are necessary to obtain a simultaneous comparison of a family of related folds. In this study, we have developed a method for multiple structure comparison largely based on sequence alignment techniques. A widely used Structural Alphabet named Protein Blocks (PBs) was used to transform the information on 3D protein backbone conformation as a 1D sequence string. A progressive alignment strategy similar to CLUSTALW was adopted for multiple PB sequence alignment (mulPBA). Highly similar stretches identified by the pairwise alignments are given higher weights during the alignment. The residue equivalences from PB based alignments are used to obtain a three dimensional fit of the structures followed by an iterative refinement of the structural superposition. Systematic comparisons using benchmark datasets of MSTAs underlines that the alignment quality is better than MULTIPROT, MUSTANG and the alignments in HOMSTRAD, in more than 85% of the cases. Comparison with other rigid-body and flexible MSTAs also indicate that mulPBA alignments are superior to most of the rigid-body MSTAs and highly comparable to the flexible alignment methods.
Published: 2012

189. Cis-trans peptide variations in structurally similar proteins

Author: Alexandre G. de Brevern, Agnel Praveen Joseph, Narayanaswamy Srinivasan, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Molecular Biophysics Unit, Indian Institute of Science, and French Ministry of Research, University of Paris Diderot - Paris 7, French National Institute for Blood Transfusion (INTS), French Institute for Health and Medical Research (INSERM), Indian Department of Biotechnology, CEFIPRA/IFCPAR for collaborative grant (number 3903-E).
Subjects: Models, Molecular, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, MESH: Sequence Homology, Amino Acid, Clinical Biochemistry, MESH: Protein Structure, Secondary, MESH: Amino Acid Sequence, 01 natural sciences, Biochemistry, Protein Structure, Secondary, cis-trans isomerization, Protein structure, cis peptides, Peptide bond, [INFO.INFO-BT]Computer Science [cs]/Biotechnology, Peptide sequence, Conserved Sequence, MESH: Structural Homology, Protein, chemistry.chemical_classification, 0303 health sciences, MESH: Conserved Sequence, MESH: Peptides, structural alignment, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Cis trans isomerization, Markov Chains, Amino acid, Folding (chemistry), Protein Blocks, structural alphabet, MESH: Models, Molecular, Proline, Stereochemistry, Structural alignment, Molecular Sequence Data, Biology, 010402 general chemistry, Article, 03 medical and health sciences, MESH: Computer Simulation, Protein Data Bank, MESH: Markov Chains, folds, Computer Simulation, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, 030304 developmental biology, MESH: Molecular Sequence Data, MESH: Proline, Sequence Homology, Amino Acid, Organic Chemistry, 0104 chemical sciences, chemistry, Structural Homology, Protein, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Peptides, Cis–trans isomerism, omega dihedral
Abstract: International audience; The presence of energetically less favourable cis peptides in protein structures has been observed to be strongly associated with its structural integrity and function. Inter-conversion between the cis and trans conformations also has an important role in the folding process. In this study, we analyse the extent of conservation of cis peptides among similar folds. We look at both the amino acid preferences and local structural changes associated with such variations. Nearly 34% of the Xaa-Proline cis bonds are not conserved in structural relatives; Proline also has a high tendency to get replaced by another amino acid in the trans conformer. At both positions bounding the peptide bond, Glycine has a higher tendency to lose the cis conformation. The cis conformation of more than 30% of β turns of type VIb and IV are not found to be conserved in similar structures. A different view using Protein Block-based description of backbone conformation, suggests that many of the local conformational changes are highly different from the general local structural variations observed among structurally similar proteins. Changes between cis and trans conformations are found to be associated with the evolution of new functions facilitated by local structural changes. This is most frequent in enzymes where new catalytic activity emerges with local changes in the active site. Cis-trans changes are also seen to facilitate inter-domain and inter-protein interactions. As in the case of folding, cis-trans conversions have been used as an important driving factor in evolution.
Published: 2012

190. Cis-trans peptide variations in structurally similar proteins.: Conservation of omega dihedral angle

Author: Joseph, Agnel Praveen, Srinivasan, Narayanaswamy, De Brevern, Alexandre, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Molecular Biophysics Unit, Indian Institute of Science, and French Ministry of Research, University of Paris Diderot - Paris 7, French National Institute for Blood Transfusion (INTS), French Institute for Health and Medical Research (INSERM), Indian Department of Biotechnology, CEFIPRA/IFCPAR for collaborative grant (number 3903-E).
Subjects: MESH: Conserved Sequence, MESH: Molecular Sequence Data, MESH: Proline, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, MESH: Peptides, MESH: Sequence Homology, Amino Acid, MESH: Protein Structure, Secondary, structural alignment, MESH: Amino Acid Sequence, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], cis-trans isomerization, MESH: Computer Simulation, cis peptides, Protein Data Bank, MESH: Markov Chains, folds, Protein Blocks, structural alphabet, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], [INFO.INFO-BT]Computer Science [cs]/Biotechnology, MESH: Models, Molecular, omega dihedral, MESH: Structural Homology, Protein
Abstract: International audience; The presence of energetically less favourable cis peptides in protein structures has been observed to be strongly associated with its structural integrity and function. Inter-conversion between the cis and trans conformations also has an important role in the folding process. In this study, we analyse the extent of conservation of cis peptides among similar folds. We look at both the amino acid preferences and local structural changes associated with such variations. Nearly 34% of the Xaa-Proline cis bonds are not conserved in structural relatives; Proline also has a high tendency to get replaced by another amino acid in the trans conformer. At both positions bounding the peptide bond, Glycine has a higher tendency to lose the cis conformation. The cis conformation of more than 30% of β turns of type VIb and IV are not found to be conserved in similar structures. A different view using Protein Block-based description of backbone conformation, suggests that many of the local conformational changes are highly different from the general local structural variations observed among structurally similar proteins. Changes between cis and trans conformations are found to be associated with the evolution of new functions facilitated by local structural changes. This is most frequent in enzymes where new catalytic activity emerges with local changes in the active site. Cis-trans changes are also seen to facilitate inter-domain and inter-protein interactions. As in the case of folding, cis-trans conversions have been used as an important driving factor in evolution.
Published: 2012

191. Prediction of enzyme activity: Implementation of the ProSAR method and assessment on experimental dataset from different sources

Author: Berland, Magali, Offmann, Bernard, André, Isabelle, Remaud Simeon, Magali, Charton, Philippe, Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA), Unité de fonctionnalité et ingénierie de protéines (UFIP), Université de Nantes - Faculté des Sciences et des Techniques, Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA), Laboratoire d'Informatique et de Mathématiques (LIM), Université de La Réunion (UR), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT), Alarcon, Nicolas, Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), and Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées
Subjects: [INFO]Computer Science [cs], [INFO] Computer Science [cs], ComputingMilieux_MISCELLANEOUS
Abstract: International audience; no abstract
Published: 2012

192. RNA sequencing revealed novel actors of the acquisition of drug resistance in Candida albicans

Author: Jean-Yves Coppée, Gaëlle Lelandais, Odile Sismeiro, Sophie Lemoine, Frédéric Devaux, Stéphane Le Crom, Rajendra Prasad, Maria Bernard, Sanjiveeni Dhamgaye, Membrane Biology Laboratory, Jawaharlal Nehru University (JNU), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Transcriptome et Epigénome (PF2), Institut Pasteur [Paris], Génomique des Microorganismes (LGM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), The work presented in this paper has been supported in part by grants to R.P. from Indo-French Center for the Promotion of Advanced Scientific Research (IFC-3403-2/2006) and DST INT/SWISS/P-31/2009., Institut de biologie de l'ENS Paris (IBENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Institut Pasteur [Paris] (IP), BMC, Ed., Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Candida albicans, beta-Glucans, lcsh:QH426-470, lcsh:Biotechnology, Repressor, RNA-Seq, Drug resistance, Multidrug resistance, Fungal Proteins, 03 medical and health sciences, Drug Resistance, Fungal, lcsh:TP248.13-248.65, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Transcriptional regulation, Genetics, CZF1, Gene, 030304 developmental biology, 0303 health sciences, biology, 030306 microbiology, Sequence Analysis, RNA, Gene Expression Profiling, biology.organism_classification, Yeast, 3. Good health, Multiple drug resistance, Gene expression profiling, lcsh:Genetics, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], RNA-seq, Biotechnology, Transcription Factors, Research Article
Abstract: Background Drug susceptible clinical isolates of Candida albicans frequently become highly tolerant to drugs during chemotherapy, with dreadful consequences to patient health. We used RNA sequencing (RNA-seq) to analyze the transcriptomes of a CDR (Candida Drug Resistance) strain and its isogenic drug sensitive counterpart. Results RNA-seq unveiled differential expression of 228 genes including a) genes previously identified as involved in CDR, b) genes not previously associated to the CDR phenotype, and c) novel transcripts whose function as a gene is uncharacterized. In particular, we show for the first time that CDR acquisition is correlated with an overexpression of the transcription factor encoding gene CZF1. CZF1 null mutants were susceptible to many drugs, independently of known multidrug resistance mechanisms. We show that CZF1 acts as a repressor of β-glucan synthesis, thus negatively regulating cell wall integrity. Finally, our RNA-seq data allowed us to identify a new transcribed region, upstream of the TAC1 gene, which encodes the major CDR transcriptional regulator. Conclusion Our results open new perspectives of the role of Czf1 and of our understanding of the transcriptional and post-transcriptional mechanisms that lead to the acquisition of drug resistance in C. albicans, with potential for future improvements of therapeutic strategies.
Published: 2012

193. Study of building intermediate states between FKBP12 and high-affinity ligands by molecular dynamics simulations

Author: Olivieri, Lilian, Laboratoire de Biochimie et Génétique Moléculaire (LBGM), Université de La Réunion (UR), Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de la Réunion, Bernard Offmann, Fabrice Gardebien, STAR, ABES, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS)
Subjects: Reconnaissance moléculaire, Fkbp12, Molecular dynamics simulations, BÉtat intermédiaire de complexationinding intermediate state, Calculs Hartree-Fock, Ligand de haute affinité, Simulations de dynamique moléculaire, État intermédiaire de complexation, Force field parameterization, Paramétrisation d’un champ de force, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular recognition, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], High-Affinity ligand, Protein-Ligand interactions, Interactions protéine-Ligand, Hartree-Fock calculations, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract: FKBP12 is an ubiquitous, mostly cytosolic, protein found at the crossroads of several signaling pathways. Its natural abundance in the nervous tissues can be related to its implication in neurodegenerative diseases like Alzheimer's and Parkinson's as well as in peripheral neuropathies and diabetes or in injuries of the spinal cords. Several studies have demonstrated that exogenous molecules (ligands) that can bind to FKBP12 allow the regeneration of many damaged neuron connections. However, there is no clear relationship between the structure of a ligand and its ability to bind to FKBP12. Our study aims at rationalizing the relationship between the structure of a ligand and its affinity to FKBP12. Two model complexes, formed between FKBP12 and each of the two high-affinity ligands 8 and 308, were studied. These two ligands are structurally different. We used molecular dynamics simulations to characterize the intermediate state that is transiently formed during the binding process between the protein and its ligand. In this state, the analysis of the nascent interactions allowed (i) to unravel the role played by the various ligand moieties in the recognition process with FKBP12 and (ii) to rationalize the affinities of related ligands., FKBP12 est une protéine ubiquitaire, principalement cytosolique, qui est au carrefour de plusieurs voies signalétiques. Son abondance naturelle dans les tissus nerveux peut être reliée à son implication dans les maladies neurodégénératives telles que les maladies d'Alzheimer et de Parkinson ainsi que dans les neuropathies périphériques et diabétiques ou dans des blessures des cordons spinaux. De nombreuses études ont montré que des molécules exogènes (ligands) venant se fixer sur cette protéine permettent la régénération d'un grand nombre de connexions neuronales endommagées. Une difficulté provient cependant du fait que, pour un ligand donné, il n'existe aucune relation claire entre sa structure et sa capacité de liaison à FKBP12. Notre étude vise ainsi à rationaliser la relation entre la structure d'un ligand et son affinité pour cette protéine. Deux complexes modèles, formés entre FKBP12 et chacun des deux ligands 8 et 308, ont été utilisés. Ces deux ligands de haute affinité ont des structures différentes. Notre travail s'est appuyé sur des simulations de dynamique moléculaire pour caractériser l'état intermédiaire qui est formé transitoirement lors du processus de complexation entre la protéine et son ligand. Dans cet état particulier, l'identification des interactions naissantes entre les partenaires a permis (i) de comprendre l'implication des différentes parties du ligand dans le mécanisme de reconnaissance avec FKBP12 et (ii) de rationaliser les affinités de certains ligands apparentés.
Published: 2012

194. Induction of Strain-Transcending Antibodies Against Group A PfEMP1 Surface Antigens from Virulent Malaria Parasites

Author: J. Alexandra Rowe, Mònica Arman, Clare Fennell, Lalla Kassambara, Ricardo Ataíde, Ogobara K. Doumbo, Michael Walther, Jean-Philippe Semblat, Yvonne Adams, Damian Nota Anong, David J. Conway, Alfred Amambua-Ngwa, Antoine Claessens, Ashfaq Ghumra, Peter C. Bull, Carolyne Kifude, Ahmed Raza, University of Edinburgh, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), University of Buéa, Université de Bamako, Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS), and Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: Male, Erythrocytes, Protozoan Proteins, Antibodies, Protozoan, Epitope, 0302 clinical medicine, Molecular Cell Biology, Malaria, Falciparum, lcsh:QH301-705.5, Pathogen, 0303 health sciences, biology, 3. Good health, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Female, Rabbits, Antibody, Research Article, lcsh:Immunologic diseases. Allergy, 030231 tropical medicine, Immunology, Plasmodium falciparum, Virulence, Antigens, Protozoan, Microbiology, 03 medical and health sciences, Antigen, Virology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], parasitic diseases, medicine, Genetics, Animals, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Molecular Biology, Biology, Africa South of the Sahara, 030304 developmental biology, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Rosette (schizont appearance), biology.organism_classification, medicine.disease, Protein Structure, Tertiary, lcsh:Biology (General), biology.protein, Parasitology, lcsh:RC581-607, Malaria
Abstract: Sequence diversity in pathogen antigens is an obstacle to the development of interventions against many infectious diseases. In malaria caused by Plasmodium falciparum, the PfEMP1 family of variant surface antigens encoded by var genes are adhesion molecules that play a pivotal role in malaria pathogenesis and clinical disease. PfEMP1 is a major target of protective immunity, however, development of drugs or vaccines based on PfEMP1 is problematic due to extensive sequence diversity within the PfEMP1 family. Here we identified the PfEMP1 variants transcribed by P. falciparum strains selected for a virulence-associated adhesion phenotype (IgM-positive rosetting). The parasites transcribed a subset of Group A PfEMP1 variants characterised by an unusual PfEMP1 architecture and a distinct N-terminal domain (either DBLα1.5 or DBLα1.8 type). Antibodies raised in rabbits against the N-terminal domains showed functional activity (surface reactivity with live infected erythrocytes (IEs), rosette inhibition and induction of phagocytosis of IEs) down to low concentrations (, Author Summary Malaria remains one of the world's most deadly diseases. Life-threatening malaria is linked to a process called rosetting, in which malaria parasite-infected red blood cells bind to uninfected red cells to form aggregates that block blood flow in vital organs such as the brain. Current efforts to develop drugs or vaccines against rosetting are hindered by variation in the parasite rosette-mediating proteins, found on the surface of infected red cells. We studied these parasite-derived surface proteins and discovered that although they are variable, they share some common features. We raised antibodies against the rosette-mediating proteins, and found that they cross-reacted with multiple rosetting parasite strains from different countries around the world, including samples collected directly from African children with severe malaria. These findings provide new insights into malaria parasite interactions with human cells, and provide proof of principle that variable parasite molecules from virulent malaria parasites can induce strain-transcending antibodies. Hence, this work provides the foundation for the development of new therapies to treat or prevent life-threatening malaria.
Published: 2012

195. Virological and epidemiological features of hepatitis delta infection among blood donors in Nouakchott, Mauritania

Author: Mohamed-Abdellahi Bollahi, Alexandra Ducancelle, Ségolène Brichler, Françoise Lunel, Michel Rosenheim, Wael Y. Mansour, Emmanuel Gordien, Frédéric Le Gal, Baidy Lô, Cheikh-Tijani Hamed, Centre national de référence des virus des hépatites B, C et Delta, Université Paris 13 (UP13)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe hospitalier Henri-Mondor, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Service de bactériologie-Virologie-Hygiène [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université des Sciences de Technologie et de Médecine (USTM), Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Groupe hospitalier Henri-Mondor, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP]
Subjects: Adult, Male, HBsAg, medicine.medical_specialty, Cirrhosis, Adolescent, Epidemiology, [SDV]Life Sciences [q-bio], viruses, Blood Donors, Virus, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, HDV, Virology, Genotype, HBV, HDV genotypes, Medicine, Humans, 030212 general & internal medicine, Hepatitis Antibodies, Phylogeny, Hepatitis B Surface Antigens, biology, business.industry, Transmission (medicine), Mauritania, virus diseases, biochemical phenomena, metabolism, and nutrition, medicine.disease, Hepatitis B, Hepatitis D, 3. Good health, Infectious Diseases, Hepatocellular carcinoma, Carrier State, Multivariate Analysis, biology.protein, 030211 gastroenterology & hepatology, Female, Antibody, Hepatitis Delta Virus, business
Abstract: International audience; BackgroundIn Mauritania, some authors have described a possible high prevalence of hepatitis delta virus (HDV) infection in the 1990s in studies of small-size samples. Objectives The aims of our study were to assess the prevalence of HDV in HBsAg positive blood donors in Mauritania, to identify the main risk factors for HDV transmission and to analyze genetic diversity of HDV strains. Study design From October 2008 to December 2009, 11,100 consecutive blood donors were considered in this study. Among them, 1700 (15.3%) were HBsAg positive and 455 accepted to participate in this study. Demographic, epidemiological, ethnical, clinical and biological data were recorded. HDV screening, i.e., antibodies (HDVAb) and RNA (HDV-RNA) detection, was performed for all of them as well as HDV and HBV genotyping. Results Ninety/455 (19.78%) donors were HDVAb positive and HDV-RNA was detectable in 56 (62.2%) of them. HDV infection was significantly associated with older age, number of marriages, military profession, residence in the desert and a history of hospitalization. The HDV genotypes of the circulating strains were HDV-1 (89.3%) and HDV-5 (10.7%). Conclusion HDV is highly endemic in Mauritanian blood donors indicating that a high number of them will develop chronic hepatitis, cirrhosis or hepatocellular carcinoma. Associated risk factors support nosocomial transmission of HDV. These data underline the need to reinforce HBV vaccination in newborns and in blood donors without HBV markers, together with screening for HDV in HBV-infected individuals.
Published: 2012

196. Prevalence, risk factors, and molecular epidemiology of hepatitis B and hepatitis delta virus in pregnant women and in patients in Mauritania

Author: Mariama Abdou Chekaraou, Françoise Lunel-Fabiani, Wael Mansour, Ahmad Sidiya, Elkhalil Ishagh, Baidy Lo, Alexandra Ducancelle, Pascal Veillon, Frédéric Le Gal, Emmanuel Gordien, Ségolène Brichler, F Zahra Fall Malick, Centre national de référence des virus des hépatites B, C et Delta, Université Paris 13 (UP13)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe hospitalier Henri-Mondor, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Service de bactériologie-Virologie-Hygiène [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université des Sciences de Technologie et de Médecine (USTM), Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Groupe hospitalier Henri-Mondor, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP]
Subjects: Adult, Male, HBsAg, medicine.medical_specialty, Blood transfusion, Adolescent, Genotype, Epidemiology, medicine.medical_treatment, viruses, [SDV]Life Sciences [q-bio], medicine.disease_cause, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Risk Factors, genotypes, Virology, Prevalence, Humans, Medicine, hepatitis Delta virus, Pregnancy Complications, Infectious, Young adult, Aged, 030304 developmental biology, Hepatitis B virus, Molecular Epidemiology, 0303 health sciences, Molecular epidemiology, business.industry, Mauritania, virus diseases, Middle Aged, Hepatitis B, medicine.disease, Hepatitis D, digestive system diseases, 3. Good health, Infectious Diseases, Female, 030211 gastroenterology & hepatology, business, Viral load, hepatitis B virus
Abstract: No recent data are available on hepatitis B virus (HBV) and hepatitis Delta virus (HDV) prevalence in Mauritania. One thousand twenty pregnant women and 946 patients visiting for routine checkups were screened for HBV and HDV infection. Demographic, epidemiological, ethnic, clinical, and biological data were recorded. HBV and HDV genotypes were determined by sequencing and phylogenetic analyses. In the pregnant women and patients cohorts, respectively, the prevalence of HBsAg (10.7% and 18.3%) and anti-HBcAb (66.3% and 76.5%) indicated high HBV endemicity. In pregnant women, exposure to HBV was significantly associated in multivariate analysis with education level, ethnicity, blood transfusion, and occupation. HDV antibodies (HDVAb) were found in 14.7% of pregnant women. In patients, HBsAg was found less frequently in females than in males. Again in multivariate analysis, exposure to HBV was significantly correlated with gender (males), and HDVAb positivity with age and gender. The HBV DNA viral load was >3 log IU/ml in only 10.1% of pregnant women and in 17.3% of patients. HDV-RNA was detectable in 21 (67.7%) of the 31 patients positive for HDVAb, and in 11 of the 16 pregnant women positive for HDVAb (68.8%). The most frequent HBV genotypes were: HBV/D, 53%; HBV/E, 35%; and HBV/A, 12%. Sub-genotyping revealed HBV/D1,/D7, and the recently described/D8. HDV genotypes were: HDV-1, 90.3% and HDV-5, 9.7%. This study confirms the high prevalence of HBV and HDV infections in Mauritania and demonstrates the high genetic diversity of HBV in this country. J. Med. Virol. 84: 1186–1198, 2012. © 2012 Wiley Periodicals, Inc.
Published: 2012

197. Local structural differences in homologous proteins: specificities in different SCOP classes

Author: Agnel Praveen Joseph, Narayanaswamy Srinivasan, Alexandre G. de Brevern, Hélène Valadié, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bioinformatique génomique et moléculaire ((U 726)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Molecular Biophysics Unit, Indian Institute of Science, and French Ministry of Research, University of Paris Diderot - Paris 7, French National Institute for Blood Transfusion (INTS), French Institute for Health and Medical Research (INSERM), Indian Department of Biotechnology, CEFIPRA/IFCPAR for collaborative grant (number 3903-E).
Subjects: Macromolecular Assemblies, Protein Folding, lcsh:Medicine, MESH: Protein Structure, Secondary, Protein Data Bank, MESH: Amino Acid Sequence, Molecular Biophysics Unit, Bioinformatics, Biochemistry, Protein Structure, Secondary, Protein structure, Macromolecular Structure Analysis, MESH: Proteins, lcsh:Science, Macromolecular Complex Analysis, protein folds, Physics, 0303 health sciences, Multidisciplinary, 030302 biochemistry & molecular biology, Protein structure prediction, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], indel, Protein Blocks, Protein folding, structural alphabet, amino acid, Research Article, Protein Structure, local structures, Biophysics, Beta helix, Sequence alignment, Computational biology, Dihedral angle, Protein Chemistry, 03 medical and health sciences, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, Protein Interactions, Biology, 030304 developmental biology, structure comparison, backbone conformation, lcsh:R, Proteins, Computational Biology, Protein superfamily, Cytoskeletal Proteins, Helix, lcsh:Q, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract: International audience; The constant increase in the number of solved protein structures is of great help in understanding the basic principles behind protein folding and evolution. 3-D structural knowledge is valuable in designing and developing methods for comparison, modelling and prediction of protein structures. These approaches for structure analysis can be directly implicated in studying protein function and for drug design. The backbone of a protein structure favours certain local conformations which include α-helices, β-strands and turns. Libraries of limited number of local conformations (Structural Alphabets) were developed in the past to obtain a useful categorization of backbone conformation. Protein Block (PB) is one such Structural Alphabet that gave a reasonable structure approximation of 0.42 Å. In this study, we use PB description of local structures to analyse conformations that are preferred sites for structural variations and insertions, among group of related folds. This knowledge can be utilized in improving tools for structure comparison that work by analysing local structure similarities. Conformational differences between homologous proteins are known to occur often in the regions comprising turns and loops. Interestingly, these differences are found to have specific preferences depending upon the structural classes of proteins. Such class-specific preferences are mainly seen in the all-β class with changes involving short helical conformations and hairpin turns. A test carried out on a benchmark dataset also indicates that the use of knowledge on the class specific variations can improve the performance of a PB based structure comparison approach. The preference for the indel sites also seem to be confined to a few backbone conformations involving β-turns and helix C-caps. These are mainly associated with short loops joining the regular secondary structures that mediate a reversal in the chain direction. Rare β-turns of type I' and II' are also identified as preferred sites for insertions.
Published: 2012

198. Local structural differences in homologous proteins: specificities in different SCOP classes

Author: Joseph, Agnel Praveen, Valadié, Hélène, Srinivasan, Narayanaswamy, De Brevern, Alexandre, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bioinformatique génomique et moléculaire ((U 726)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Molecular Biophysics Unit, Indian Institute of Science, and French Ministry of Research, University of Paris Diderot - Paris 7, French National Institute for Blood Transfusion (INTS), French Institute for Health and Medical Research (INSERM), Indian Department of Biotechnology, CEFIPRA/IFCPAR for collaborative grant (number 3903-E).
Subjects: structure comparison, local structures, backbone conformation, MESH: Protein Structure, Secondary, Protein Data Bank, MESH: Amino Acid Sequence, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], indel, Protein Blocks, structural alphabet, MESH: Proteins, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], amino acid, protein folds
Abstract: International audience; The constant increase in the number of solved protein structures is of great help in understanding the basic principles behind protein folding and evolution. 3-D structural knowledge is valuable in designing and developing methods for comparison, modelling and prediction of protein structures. These approaches for structure analysis can be directly implicated in studying protein function and for drug design. The backbone of a protein structure favours certain local conformations which include α-helices, β-strands and turns. Libraries of limited number of local conformations (Structural Alphabets) were developed in the past to obtain a useful categorization of backbone conformation. Protein Block (PB) is one such Structural Alphabet that gave a reasonable structure approximation of 0.42 Å. In this study, we use PB description of local structures to analyse conformations that are preferred sites for structural variations and insertions, among group of related folds. This knowledge can be utilized in improving tools for structure comparison that work by analysing local structure similarities. Conformational differences between homologous proteins are known to occur often in the regions comprising turns and loops. Interestingly, these differences are found to have specific preferences depending upon the structural classes of proteins. Such class-specific preferences are mainly seen in the all-β class with changes involving short helical conformations and hairpin turns. A test carried out on a benchmark dataset also indicates that the use of knowledge on the class specific variations can improve the performance of a PB based structure comparison approach. The preference for the indel sites also seem to be confined to a few backbone conformations involving β-turns and helix C-caps. These are mainly associated with short loops joining the regular secondary structures that mediate a reversal in the chain direction. Rare β-turns of type I' and II' are also identified as preferred sites for insertions.
Published: 2012

199. Molecular characteristics of Human Endogenous Retrovirus type-W in schizophrenia and bipolar disorder

Author: Perron, Hervé, Hamdani, Nora, Faucard, Raphaël, Lajnef, Mohamed, Jamain, Stéphane, Daban-Huard, Claire, Sarrazin, Samuel, Leguen, Emmanuel, Houenou, Josselin, Delavest, Marine, Moins-Teiserenc, Hélène, Bengoufa, Djaouida, Yolken, Robert, Madeira, Alexandra, Garcia-Montojo, Marta, Gehin, Nadège, Burgelin, Ingrid, Ollagnier, Guillaume, Bernard, Corinne, Dumaine, Anne, Henrion, Annabelle, Gombert, Anaïs, Le Dudal, Katia, Charron, Dominique, Krishnamoorthy, Rajagopal, Tamouza, Ryad, Leboyer, Marion, Guellaen, Georges, Geneuro, GeNeuro, Geneuro-Innovation, Université de Lyon, Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Fondation FondaMental [Créteil], IFR49 - Neurospin - CEA, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hématologie -Immunologie -Cibles thérapeutiques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Stanley Laboratory of Developmental Neurovirology, Johns Hopkins University Medical Center, Plateforme de Ressources Biologiques, Stanley Research Program, CIC - CHU Henri Mondor, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by the Institut National pour la Recherche Médicale (INSERM), France, the Assistance Publique des Hôpitaux de Paris (AP-HP) , France, and the Agence Nationale pour la Recherche (ANR - Project V .I.P.) , France and the Réseau Thématique de Recherche et de Soin en Santé Mentale, Fondation FondaMental, France.
Subjects: Bipolar Disorder, HERV-W, viruses, MSRV, embryonic structures, CNV, Schizophrenia, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Toxoplasma
Abstract: International audience; Epidemiological and genome-wide association studies of severe psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD), suggest complex interactions between multiple genetic elements and environmental factors. The involvement of genetic elements such as Human Endogenous Retroviruses type 'W' family (HERV-W) has consistently been associated with SZ. HERV-W envelope gene (env) is activated by environmental factors and encodes a protein displaying inflammation and neurotoxicity. The present study addressed the molecular characteristics of HERV-W env in SZ and BD. Hundred and thirty-six patients, 91 with BD, 45 with SZ and 73 healthy controls (HC) were included. HERV-W env transcription was found to be elevated in BD (P
Published: 2012

200. Comparison of tertiary structures of proteins in protein-protein complexes with unbound forms suggests prevalence of allostery in signalling proteins

Author: Alexandre G. de Brevern, Narayanaswamy Srinivasan, Swapnil Mahajan, Lakshmipuram S. Swapna, Molecular Biophysics Unit, Indian Institute of Science, Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), This research is supported by Indo-French collaborative grant (CEFIPRA/IFCPAR number 3903-E) between AdB and NS. Part of this project is also supported for NS by Department of Biotechnology (DBT). Part of this was supported for AdB by grants from the Ministry of Research, University Paris Diderot - Paris 7, National Institute for Blood Transfusion (INTS) and the Institute for Health and Medical Research (INSERM)., and BMC, Ed.
Subjects: Models, Molecular, MESH: Databases, Protein, MESH: Signal Transduction, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Allosteric regulation, Computational biology, Biology, Molecular Biophysics Unit, Ligands, 03 medical and health sciences, MESH: Protein Structure, Tertiary, Structural Biology, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Ligands, Animals, MESH: Protein Binding, MESH: Animals, MESH: Proteins, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Databases, Protein, MESH: Allosteric Site, lcsh:QH301-705.5, 030304 developmental biology, 0303 health sciences, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Protein protein, 030302 biochemistry & molecular biology, Proteins, computer.file_format, Protein Data Bank, Protein Structure, Tertiary, Signalling, Biochemistry, lcsh:Biology (General), Functional significance, computer, Allosteric Site, MESH: Models, Molecular, Protein Binding, Signal Transduction, Research Article
Abstract: Background Most signalling and regulatory proteins participate in transient protein-protein interactions during biological processes. They usually serve as key regulators of various cellular processes and are often stable in both protein-bound and unbound forms. Availability of high-resolution structures of their unbound and bound forms provides an opportunity to understand the molecular mechanisms involved. In this work, we have addressed the question “What is the nature, extent, location and functional significance of structural changes which are associated with formation of protein-protein complexes?” Results A database of 76 non-redundant sets of high resolution 3-D structures of protein-protein complexes, representing diverse functions, and corresponding unbound forms, has been used in this analysis. Structural changes associated with protein-protein complexation have been investigated using structural measures and Protein Blocks description. Our study highlights that significant structural rearrangement occurs on binding at the interface as well as at regions away from the interface to form a highly specific, stable and functional complex. Notably, predominantly unaltered interfaces interact mainly with interfaces undergoing substantial structural alterations, revealing the presence of at least one structural regulatory component in every complex. Interestingly, about one-half of the number of complexes, comprising largely of signalling proteins, show substantial localized structural change at surfaces away from the interface. Normal mode analysis and available information on functions on some of these complexes suggests that many of these changes are allosteric. This change is largely manifest in the proteins whose interfaces are altered upon binding, implicating structural change as the possible trigger of allosteric effect. Although large-scale studies of allostery induced by small-molecule effectors are available in literature, this is, to our knowledge, the first study indicating the prevalence of allostery induced by protein effectors. Conclusions The enrichment of allosteric sites in signalling proteins, whose mutations commonly lead to diseases such as cancer, provides support for the usage of allosteric modulators in combating these diseases.
Published: 2012

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Journal

Database

Publisher

608 results on '"Institut National de la Transfusion Sanguine [Paris] (INTS)"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources