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3. The inhibition of assembly of HIV-1 virus-like particles by 3-O-(3',3'-dimethylsuccinyl) betulinic acid (DSB) is counteracted by Vif and requires its Zinc-binding domain

Author

Bouaziz Serge, Hong Saw, Gay Bernard, Coric Pascale, DaFonseca Sandrina, and Boulanger Pierre

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background DSB, the 3-O-(3',3'dimethylsuccinyl) derivative of betulinic acid, blocks the last step of protease-mediated processing of HIV-1 Gag precursor (Pr55Gag), which leads to immature, noninfectious virions. When administered to Pr55Gag-expressing insect cells (Sf9), DSB inhibits the assembly and budding of membrane-enveloped virus-like particles (VLP). In order to explore the possibility that viral factors could modulate the susceptibility to DSB of the VLP assembly process, several viral proteins were coexpressed individually with Pr55Gag in DSB-treated cells, and VLP yields assayed in the extracellular medium. Results Wild-type Vif (Vifwt) restored the VLP production in DSB-treated cells to levels observed in control, untreated cells. DSB-counteracting effect was also observed with Vif mutants defective in encapsidation into VLP, suggesting that packaging and anti-DSB effect were separate functions in Vif. The anti-DSB effect was abolished for VifC133S and VifS116V, two mutants which lacked the zinc binding domain (ZBD) formed by the four H108C114C133H139 coordinates with a Zn atom. Electron microscopic analysis of cells coexpressing Pr55Gag and Vifwt showed that a large proportion of VLP budded into cytoplasmic vesicles and were released from Sf9 cells by exocytosis. However, in the presence of mutant VifC133S or VifS116V, most of the VLP assembled and budded at the plasma membrane, as in control cells expressing Pr55Gag alone. Conclusion The function of HIV-1 Vif protein which negated the DSB inhibition of VLP assembly was independent of its packaging capability, but depended on the integrity of ZBD. In the presence of Vifwt, but not with ZBD mutants VifC133S and VifS116V, VLP were redirected to a vesicular compartment and egressed via the exocytic pathway.

Published
2008
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4. Direct Vpr-Vpr Interaction in Cells monitored by two Photon Fluorescence Correlation Spectroscopy and Fluorescence Lifetime Imaging

Author

Mély Yves, Darlix Jean-Luc, Bouaziz Serge, Morellet Nelly, Cabanne Charlotte, Muriaux Delphine, Schaub Emmanuel, Clamme Jean-Pierre, Didier Pascal, Fritz Joëlle V, and de Rocquigny Hugues

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background The human immunodeficiency virus type 1 (HIV-1) encodes several regulatory proteins, notably Vpr which influences the survival of the infected cells by causing a G2/M arrest and apoptosis. Such an important role of Vpr in HIV-1 disease progression has fuelled a large number of studies, from its 3D structure to the characterization of specific cellular partners. However, no direct imaging and quantification of Vpr-Vpr interaction in living cells has yet been reported. To address this issue, eGFP- and mCherry proteins were tagged by Vpr, expressed in HeLa cells and their interaction was studied by two photon fluorescence lifetime imaging microscopy and fluorescence correlation spectroscopy. Results Results show that Vpr forms homo-oligomers at or close to the nuclear envelope. Moreover, Vpr dimers and trimers were found in the cytoplasm and in the nucleus. Point mutations in the three α helices of Vpr drastically impaired Vpr oligomerization and localization at the nuclear envelope while point mutations outside the helical regions had no effect. Theoretical structures of Vpr mutants reveal that mutations within the α-helices could perturb the leucine zipper like motifs. The ΔQ44 mutation has the most drastic effect since it likely disrupts the second helix. Finally, all Vpr point mutants caused cell apoptosis suggesting that Vpr-mediated apoptosis functions independently from Vpr oligomerization. Conclusion We report that Vpr oligomerization in HeLa cells relies on the hydrophobic core formed by the three α helices. This oligomerization is required for Vpr localization at the nuclear envelope but not for Vpr-mediated apoptosis.

Published
2008
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5. Localization of HIV-1 Vpr to the nuclear envelope: Impact on Vpr functions and virus replication in macrophages

Author

Bouaziz Serge, Bouchet Jérôme, Mazzolini Julie, David Annie, Le Rouzic Erwann, Jacquot Guillaume, Niedergang Florence, Pancino Gianfranco, and Benichou Serge

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background HIV-1 Vpr is a dynamic protein that primarily localizes in the nucleus, but a significant fraction is concentrated at the nuclear envelope (NE), supporting an interaction between Vpr and components of the nuclear pore complex, including the nucleoporin hCG1. In the present study, we have explored the contribution of Vpr accumulation at the NE to the Vpr functions, including G2-arrest and pro-apoptotic activities, and virus replication in primary macrophages. Results In order to define the functional role of Vpr localization at the NE, we have characterized a set of single-point Vpr mutants, and selected two new mutants with substitutions within the first α-helix of the protein, Vpr-L23F and Vpr-K27M, that failed to associate with hCG1, but were still able to interact with other known relevant host partners of Vpr. In mammalian cells, these mutants failed to localize at the NE resulting in a diffuse nucleocytoplasmic distribution both in HeLa cells and in primary human monocyte-derived macrophages. Other mutants with substitutions in the first α-helix (Vpr-A30L and Vpr-F34I) were similarly distributed between the nucleus and cytoplasm, demonstrating that this helix contains the determinants required for localization of Vpr at the NE. All these mutations also impaired the Vpr-mediated G2-arrest of the cell cycle and the subsequent cell death induction, indicating a functional link between these activities and the Vpr accumulation at the NE. However, this localization is not sufficient, since mutations within the C-terminal basic region of Vpr (Vpr-R80A and Vpr-R90K), disrupted the G2-arrest and apoptotic activities without altering NE localization. Finally, the replication of the Vpr-L23F and Vpr-K27M hCG1-binding deficient mutant viruses was also affected in primary macrophages from some but not all donors. Conclusion These results indicate that the targeting of Vpr to the nuclear pore complex may constitute an early step toward Vpr-induced G2-arrest and subsequent apoptosis; they also suggest that Vpr targeting to the nuclear pore complex is not absolutely required, but can improve HIV-1 replication in macrophages.

Published
2007
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11. The Copying of Complex Geometric Drawings by Sighted and Visually Impaired Children

Author

Bouaziz, Serge, Russier, Sandrine, and Magnan, Annie

Abstract

This study examined the role of visual imagery in the centripetal execution principle (CEP), a graphic rule that is related to the drawing of complex figures that are composed of embedded geometric shapes. Sighted blindfolded children and children with early-onset low vision and early-onset blindness copied raised-line drawings (using only the haptic modality). The results revealed the dominance of the CEP in the sighted and blind groups, but not in the group with low vision. They suggest that the CEP is not determined by visual imagery, but by a more general mechanism that is based on children's perceptual experience.

Published
2005

19. Contribution of the Visual Perception and Graphic Production Systems to the Copying of Complex Geometrical Drawings: A Developmental Study

Author

Bouaziz, Serge and Magnan, Annie

Abstract

The aim of this study was to determine the contribution of the visual perception and graphic production systems [Van Sommers, P. (1989). "A system for drawing and drawing-related neuropsychology." "Cognitive Neuropsychology," 6, 117-164] to the manifestation of the "Centripetal Execution Principle" (CEP), a graphic rule for the copying of drawings consisting of embedded simple geometric shapes from the outside shape to the inside shape. Children aged 4-8 years copied two types of model that differed in the visual salience of one of the simple geometric shapes (drawn in bold or normal weight lines), producing the drawings either by graphic execution (freehand) or by superimposing the simple geometric shapes. The results indicated that the frequency of CEP depended both on the type of model and on the drawing context in the youngest children. They suggest that the CEP is determined by the structure of the representation of the models and the planning of the execution of the drawings. The developmental differences in the effects of visual salience and execution context are discussed in the light of the development of representational flexibility and planning abilities. These data are consistent with a dissociation between the visual perception and graphic production systems and account for their interaction.

Published
2007
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22. Mixed Polymeric Micelles for Rapamycin Skin Delivery

Author

Le Guyader, Guillaume, primary, Do, Bernard, additional, Rietveld, Ivo B., additional, Coric, Pascale, additional, Bouaziz, Serge, additional, Guigner, Jean-Michel, additional, Secretan, Philippe-Henri, additional, Andrieux, Karine, additional, and Paul, Muriel, additional

Published
2022
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23. Two-long terminal repeat (LTR) DNA circles are a substrate for HIV-1 integrase

Author

Chaignepain, Stephane, Maillot, Benoit, Oladosu, Oyindamola, Robert, Xavier, Fiorini, Francesca, Kieffer, Bruno, Bouaziz, Serge, Gouet, Patrice, Ruff, Marc, Lee, Ga-Eun, Mauro, Eric, Shin, Cha-Gyun, Richetta, Clémence, Thierry, Sylvain, Thierry, Eloise, Lesbats, Paul, Lapaillerie, Delphine, Munir, Soundasse, Subra, Frédéric, Leh, Hervé, Deprez, Eric, Parissi, Vincent, Delelis, Olivier, Immunité infection vaccination (I2V), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre génomique fonctionnelle, Université Bordeaux Segalen - Bordeaux 2, Department of Microbiology, Kohat University of Science and Technology (KUST), Laboratoire de Biotechnologie et Pharmacogénétique Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Bioalliancepharma, and Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA)

Subjects
0301 basic medicine, Virus Integration, [SDV]Life Sciences [q-bio], HIV Integrase, Microbiology, Biochemistry, law.invention, 03 medical and health sciences, chemistry.chemical_compound, Retrovirus, law, Humans, Molecular Biology, ComputingMilieux_MISCELLANEOUS, HIV Long Terminal Repeat, 030102 biochemistry & molecular biology, biology, Chemistry, Cell Biology, Integrases, biology.organism_classification, Reverse transcriptase, Long terminal repeat, 3. Good health, Integrase, Cell biology, 030104 developmental biology, Viral replication, DNA, Viral, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, biology.protein, Recombinant DNA, DNA, Circular, DNA
Abstract

Integration of the HIV-1 DNA into the host genome is essential for viral replication and is catalyzed by the retroviral integrase. To date, the only substrate described to be involved in this critical reaction is the linear viral DNA produced in reverse transcription. However, during HIV-1 infection, two-long terminal repeat DNA circles (2-LTRcs) are also generated through the ligation of the viral DNA ends by the host cell's nonhomologous DNA end-joining pathway. These DNAs contain all the genetic information required for viral replication, but their role in HIV-1's life cycle remains unknown. We previously showed that both linear and circular DNA fragments containing the 2-LTR palindrome junction can be efficiently cleaved in vitro by recombinant integrases, leading to the formation of linear 3′-processed–like DNA. In this report, using in vitro experiments with purified proteins and DNAs along with DNA endonuclease and in vivo integration assays, we show that this circularized genome can also be efficiently used as a substrate in HIV-1 integrase-mediated integration both in vitro and in eukaryotic cells. Notably, we demonstrate that the palindrome cleavage occurs via a two-step mechanism leading to a blunt-ended DNA product, followed by a classical 3′-processing reaction; this cleavage leads to integrase-dependent integration, highlighted by a 5-bp duplication of the host genome. Our results suggest that 2-LTRc may constitute a reserve supply of HIV-1 genomes for proviral integration.

Published
2019
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26. Acetonitrile allows indirect replacement of non‐deuterated lipid detergents by deuterated lipid detergents for the NMR study of detergent‐soluble proteins

Author

Wang, Xiao, Chen, Xiaowei, Bouaziz, Serge, Nonin-Lecomte, Sylvie, Cibles Thérapeutiques et conception de médicaments (CiTCoM - UMR 8038), and Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)

Subjects
acetonitrile, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], DPC-to-protein molar ratio, 3D structure, detergent-soluble proteins, NMR
Abstract

International audience; Detergent-soluble proteins (DSPs) are commonly dissolved in lipid buffers for NMR experiments, but the huge lipid proton signal prevents recording of high-quality spectra. The use of costly deuterated lipids is thus required to replace non-deuterated ones. With conventional methods, detergents like dodecylphosphocholine (DPC) cannot be fully exchanged due to their high binding affinity to hydrophobic proteins. We propose an original and simple protocol which combines the use of acetonitrile, dialysis and lyophilization to disrupt the binding of lipids to the protein and allow their indirect replacement by their deuterated equivalents, while maintaining the native structure of the protein. Moreover, by this protocol, the detergent-to-protein molar ratio can be controlled as it challenges the protein structure. This protocol was applied to solubilize the Vpx protein that was followed upon addition of DPC-d38 by 1H-15N SOFAST-HMQC spectra and the best detergent-to-DSPs molar ratio was obtained for structural studies.

Published
2021
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27. Genuine Selective Caspase-2 Inhibition with new Irreversible Small Peptidomimetics

Author

Bosc, Elodie, primary, Anastasie, Julie, additional, Soualmia, Feryel, additional, Coric, Pascale, additional, Kim, Ju Youn, additional, Lacin, Gullen, additional, Duplus, Eric, additional, Tixador, Philippe, additional, Brugg, Bernard, additional, Reboud-Ravaux, Michelle, additional, Bouaziz, Serge, additional, Karin, Michael, additional, El Amri, Chahrazade, additional, and Jacotot, Etienne, additional

Published
2021
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28. Capsicumicine, a New Bioinspired Peptide from Red Peppers Prevents Staphylococcal Biofilm In Vitro and In Vivo via a Matrix Anti-Assembly Mechanism of Action

Author

Gomes Von Borowski, Rafael, primary, Chat, Sophie, additional, Schneider, Rafael, additional, Nonin-Lecomte, Sylvie, additional, Bouaziz, Serge, additional, Giudice, Emmanuel, additional, Rigon Zimmer, Aline, additional, Baggio Gnoatto, Simone Cristina, additional, Macedo, Alexandre José, additional, and Gillet, Reynald, additional

Published
2021
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32. Accurate nanoscale flexibility measurement of DNA and DNA–protein complexes by atomic force microscopy in liquid

Author

Murugesapillai, Divakaran, Bouaziz, Serge, Maher, L James, Israeloff, Nathan, Cameron, Craig, Williams, Mark, Maher, L. James, Bouaziz, Serge, Unité de Pharmacologie Chimique et Génétique (UPCG - UMR_S 640/UMR 8151), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)

Subjects
0301 basic medicine, Saccharomyces cerevisiae Proteins, Materials science, Optical Tweezers, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Analytical chemistry, Protein dna, Microscopy, Atomic Force, MESH: vpr Gene Products, Human Immunodeficiency Virus, Quantitative Biology::Subcellular Processes, 03 medical and health sciences, chemistry.chemical_compound, MESH: Saccharomyces cerevisiae Proteins, Molecule, MESH: Proteins, General Materials Science, Elasticity (economics), Nanoscopic scale, MESH: Microscopy, Atomic Force, Persistence length, Quantitative Biology::Biomolecules, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Atomic force microscopy, technology, industry, and agriculture, High Mobility Group Proteins, MESH: DNA, Proteins, DNA, vpr Gene Products, Human Immunodeficiency Virus, MESH: High Mobility Group Proteins, Quantitative Biology::Genomics, Elasticity, Condensed Matter::Soft Condensed Matter, MESH: Optical Tweezers, Chemistry, 030104 developmental biology, Optical tweezers, chemistry, Chemical physics, MESH: Elasticity
Abstract

We obtain accurate three-dimensional persistence length measurements for DNA and DNA–protein complexes using liquid AFM imaging, validated by optical tweezers., The elasticity of double-stranded DNA (dsDNA), as described by its persistence length, is critical for many biological processes, including genomic regulation. A persistence length value can be obtained using atomic force microscopy (AFM) imaging. However, most AFM studies have been done by depositing the sample on a surface using adhesive ligands and fitting the contour to a two-dimensional (2D) wormlike chain (WLC) model. This often results in a persistence length measurement that is different from the value determined using bulk and single molecule methods. We describe a method for obtaining accurate three-dimensional (3D) persistence length measurements for DNA and DNA–protein complexes by using a previously developed liquid AFM imaging method and then applying the 3D WLC model. To demonstrate the method, we image in both air and liquid several different dsDNA constructs and DNA–protein complexes that both increase (HIV-1 Vpr) and decrease (yeast HMO1) dsDNA persistence length. Fitting the liquid AFM-imaging contour to the 3D WLC model results in a value in agreement with measurements obtained in optical tweezers experiments. Because AFM also allows characterization of local DNA properties, the ability to correctly measure global flexibility will strongly increase the impact of measurements that use AFM imaging.

Published
2017
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33. Guttiferone A Aggregates Modulate Silent Information Regulator 1 (SIRT1) Activity

Author

Cottet, Kévin, Xu, Bin, Coric, Pascale, Bouaziz, Serge, Michel, Michel, Vidal, Michel, Lallemand, Marie-Christine, Broussy, Sylvain, Michel, Sylvie, Yangtze Delta Region Institute of Tsinghua University [Zhejiang], Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Unité de Pharmacologie Chimique et Génétique (UPCG - UMR_S 640/UMR 8151), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Equipe Pharmacognosie (UMR 8638), Chimie Organique, Médicinale et Extractive et Toxicologie Expérimentale (COMETE - UMR 8638), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Paris Descartes - Paris 5 (UPD5), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Mécanique et Technologie (LMT), École normale supérieure - Cachan (ENS Cachan)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), and Bouaziz, Serge

Subjects
Models, Molecular, 0301 basic medicine, MESH: Benzophenones, Magnetic Resonance Spectroscopy, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], MESH: Biological Products, MESH: Molecular Structure, Regulator, MESH: Dynamic Light Scattering, MESH: Dose-Response Relationship, Drug, Benzophenones, Structure-Activity Relationship, 03 medical and health sciences, chemistry.chemical_compound, MESH: Structure-Activity Relationship, Sirtuin 1, Clusiaceae, Drug Discovery, Humans, Structure–activity relationship, MESH: Sirtuin 1, Enzyme Inhibitors, chemistry.chemical_classification, Biological Products, MESH: Humans, Natural product, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Dose-Response Relationship, Drug, Molecular Structure, MESH: Magnetic Resonance Spectroscopy, Nuclear magnetic resonance spectroscopy, Dynamic Light Scattering, In vitro, 3. Good health, MESH: Clusiaceae, Hyperforin, 030104 developmental biology, Enzyme, chemistry, Biochemistry, MESH: Enzyme Inhibitors, Biological target, Molecular Medicine, MESH: Models, Molecular
Abstract

International audience; Natural products guttiferone A, hyperforin, and aristoforin were able to inhibit or increase SIRT1 catalytic activity, depending on protein concentration and presence of detergent. On the basis of NMR data for guttiferone A, we demonstrated that the aggregation state of the natural product played a crucial role for its interaction with the enzyme. These results are useful to interpret future in vitro structure-activity relationship studies on these natural products in the quest of their biological target(s).

Published
2016
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37. 1H and 15N resonance assignment and secondary structure of capsicein, an alpha-elicitin, determined by three-dimensional heteronuclear NMR

Author

Bouaziz, Serge, Heijenoort, Carine van, Huet, Jean-Claude, Pernollet, Jean-Claude, and Guittet, Eric

Subjects
Proteins -- Research, Phospholipases -- Research, Plasma membranes -- Research, Biological sciences, Chemistry
Abstract

3D heteronuclear NMR reveals all the proton and 15N resonances in the study of a protein capsicein for which X-ray data of structural knowledge is absent. 15N labeling of capsicein by numerous overlaps helps study the interaction of the protein with lipids and membranes. The C-terminal secondary structure motifs of capsicein exhibit phospholipase structural features suggesting that elicitin directly interacts with the lipids of the plasma membrane.

Published
1994

38. Synthesis and characterization of water-soluble macrocyclic peptides stabilizing protein α-turn

Author

Wang, Lei, Coric, Pascale, Zhu, Kexin, Liu, Wang-Qing, Vidal, Michel, Bouaziz, Serge, Broussy, Sylvain, Wang, Wang-Qing, Bouaziz, Serge, Science & Technology Information Institute, Shandong Academy of Agricultural Science, Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Pharmacochimie Moléculaire et Cellulaire (PMC - UMR_S 648), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Pharmacologie Chimique et Génétique (UPCG - UMR_S 640/UMR 8151), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Protein Conformation, alpha-Helical, Stereochemistry, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Peptide, Chemistry Techniques, Synthetic, Molecular Dynamics Simulation, 010402 general chemistry, 01 natural sciences, Biochemistry, Peptides, Cyclic, Turn (biochemistry), Protein structure, MESH: Protein Stability, Side chain, MESH: Water, MESH: Molecular Dynamics Simulation, MESH: Hydrogen Bonding, Physical and Theoretical Chemistry, Conformational isomerism, MESH: Peptides, Cyclic, chemistry.chemical_classification, MESH: Protein Conformation, alpha-Helical, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], 010405 organic chemistry, Chemistry, Hydrogen bond, MESH: Peptides, Protein Stability, Organic Chemistry, Water, Hydrogen Bonding, 0104 chemical sciences, Amino acid, MESH: Solubility, Solubility, Covalent bond, MESH: Chemistry Techniques, Synthetic, Peptides
Abstract

International audience; Short peptides composed of naturally occurring amino acids are usually unstructured in aqueous media. The installation of covalent constraints within their side chains or backbones, resulting in the formation of macrocyclic peptides, is an appealing approach to stabilize them in defined secondary structures. Therefore, with the objective to stabilize α-turn conformation, we designed, synthesized and characterized constrained 13-membered macrocyclic peptides. Their design was inspired by previous work using the replacement of a hydrogen bond by a covalent bond, for the stabilization of α-helical secondary structures. Their synthesis employed our recently published solid-phase method based on Fukuyama-Mitsunobu alkylation reactions. We report herein an optimized synthesis leading to three water-soluble 13-membered macrocyclic peptides 10a-c, including respectively two, one and zero glycine residues. They were characterized by CD and NMR, which indicated the presence of equilibrating conformers. The detailed conformational analysis was based on extensive NMR and molecular dynamics studies. We found that the peptide without glycine residues 10c was mostly present as slowly interconverting conformers whereas the peptide with two glycine residues 10a was mostly present as rapidly interconverting conformers. We did not find a good match between the conformers of 10a and α-turns occurring in proteins, due to the high flexibility of the glycine backbone. Interestingly, we found that the major conformer of 10c accurately matched the "non-classical" or "tight" α-turn of type II-αLS, with a RMSD value of 0.42 Å for heavy atoms constituting the macrocycle. This is, to the best of our knowledge, the first molecule reported to mimic this type of α-turn found in proteins.

Published
2017
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39. Nuclear Magnetic Resonance Structure of the Human Polyoma JC Virus Agnoprotein

Author

Coric, Pascale, Saribas, A Sami, Abou-Gharbia, Magid, Childers, Wayne, Condra, Jon, White, Martyn, Safak, Mahmut, Bouaziz, Serge, Saribas, A. Sami, Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Unité de Pharmacologie Chimique et Génétique (UPCG - UMR_S 640/UMR 8151), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Bouaziz, Serge

Subjects
0301 basic medicine, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Stereochemistry, Viral protein, ALPHA-HELIX, JC virus, MESH: JC Virus, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY, MESH: Protein Structure, Secondary, Peptide, medicine.disease_cause, Biochemistry, Oligomer, Protein Structure, Secondary, Article, 03 medical and health sciences, chemistry.chemical_compound, SV40, MESH: Nuclear Magnetic Resonance, Biomolecular, medicine, Humans, Viral Regulatory and Accessory Proteins, Nuclear Magnetic Resonance, Biomolecular, Molecular Biology, chemistry.chemical_classification, BKV, DIMER, MESH: Humans, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], INTRINSICALLY UNSTRUCTURED, POLYOMAVIRUS, OLIGOMER, Cell Biology, DNA, JC Virus, AGNOPROTEIN, MERKEL CELL, NMR, 3. Good health, Amino acid, JCV, 030104 developmental biology, chemistry, Viral replication, REPLICATION, Alpha helix, MESH: Viral Regulatory and Accessory Proteins
Abstract

International audience; Agnoprotein is an important regulatory protein of the human polyoma JC virus (JCV) and plays critical roles during the viral replication cycle. It forms highly stable dimers and oligomers through its Leu/Ile/Phe-rich domain, which is important for the stability and function of the protein. We recently resolved the partial 3D structure of this protein by NMR using a synthetic peptide encompassing amino acids Thr17 to Gln52, where the Leu/Ile/Phe- rich region was found to adopt a major alpha-helix conformation spanning amino acids 23-39. Here, we report the resolution of the 3D structure of full-length JCV agnoprotein by NMR, which not only confirmed the existence of the previously reported major α-helix domain at the same position but also revealed the presence of an additional minor α-helix region spanning amino acid residues Leu6 to lys13. The remaining regions of the protein adopt an intrinsically unstructured conformation. J. Cell. Biochem. 118: 3268-3280, 2017. © 2017 Wiley Periodicals, Inc.

Published
2017
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40. 1H, 13C and 15N backbone resonance assignment of HIV-1 Gag (276–432) encompassing the C-terminal domain of the capsid protein, the spacer peptide 1 and the nucleocapsid protein.

Author

Chen, Xiaowei, Coric, Pascale, and Bouaziz, Serge

Abstract

During the maturation of the HIV-1 particle, the Gag polyprotein is cleaved by the viral protease into several proteins: matrix (MA), capsid (CA), spacer peptide 1 (SP1), nucleocapsid (NC), spacer peptide 2 (SP2) and p6. After cleavage, these proteins rearrange to form infectious viral particles. The final cleavage by the protease occurs between CA and SP1 and is the limiting step for the maturation of the particle. The CA–SP1 junction is the target of HIV-1 maturation inhibitors. CA is responsible for the formation of the viral capsid which protects the viral RNA inside. The SP1 domain is essential for viral assembly and infectivity, it is flexible and in helix-coil equilibrium. The presence of NC allows the SP1 domain to be less dynamic. The perturbation of the natural coil-helix equilibrium to helix interferes with protease cleavage and leads to non-completion of viral maturation. In this work, two mutations, W316A and M317A, that abolish the oligomerization of CA were introduced into the protein. The HIV-1 CACTDW316A, M317A-SP1-NC which contains the C-terminal monomeric mutant of CA, SP1 and NC was produced to study the mechanism of action of HIV-1 maturation inhibitors. Here we report the backbone assignment of the protein CACTDW316A, M317A-SP1-NC. These results will be useful to study the interaction between HIV-1 Gag and HIV-1 maturation inhibitors. [ABSTRACT FROM AUTHOR]

Published
2021
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41. Reconciling NMR Structures of the HIV-1 Nucleocapsid Protein NCp7 Using Extensive Polarizable Force Field Free-Energy Simulations

Author

El Khoury, Léa, primary, Célerse, Frédéric, additional, Lagardère, Louis, additional, Jolly, Luc-Henri, additional, Derat, Etienne, additional, Hobaika, Zeina, additional, Maroun, Richard G., additional, Ren, Pengyu, additional, Bouaziz, Serge, additional, Gresh, Nohad, additional, and Piquemal, Jean-Philip, additional

Published
2020
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42. HIV-1 Pre-Integration Complexes. Structures, Functions and Drug Design

Author

Batisse, Julien, primary, Bruch, Eduardo, additional, Levy, Nicolas, additional, Eiler, Sylvia, additional, Duclaud, Sylvie, additional, Schultz, Patrick, additional, Gouet, Patrice, additional, Bouaziz, Serge, additional, Delelis, Olivier, additional, Parissi, Vincent, additional, and Ruff, Marc, additional

Published
2020
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43. Reconciling NMR Structures of the HIV-1 Nucleocapsid Protein (NCp7) using Extensive Polarizable Force Field Free-Energy Simulations

Author

El Khoury, Léa, primary, Célerse, Frédéric, additional, Lagardere, Louis, additional, Jolly, Luc-Henri, additional, Derat, Étienne, additional, Hobaika, Zeina, additional, G. Maroun, Richard, additional, Ren, Pengyu, additional, Bouaziz, Serge, additional, Gresh, Nohad, additional, and Piquemal, Jean-Philip, additional

Published
2019
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45. Human H4 tail stimulates HIV-1 integration through binding to the carboxy-terminal domain of integrase

Author

Mauro, Eric, primary, Lesbats, Paul, additional, Lapaillerie, Delphine, additional, Chaignepain, Stephane, additional, Maillot, Benoit, additional, Oladosu, Oyindamola, additional, Robert, Xavier, additional, Fiorini, Francesca, additional, Kieffer, Bruno, additional, Bouaziz, Serge, additional, Gouet, Patrice, additional, Ruff, Marc, additional, and Parissi, Vincent, additional

Published
2019
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48. Biophysical Studies of the Induced Dimerization of Human VEGF Receptor 1 Binding Domain by Divalent Metals Competing with VEGF-A

Author

Gaucher, Jean-François, Reille-Seroussi, Marie, Gagey-Eilstein, Nathalie, Broussy, Sylvain, Coric, Pascale, Seijo, Bili, Lascombe, Marie-Bernard, Gautier, Benoît, Liu, Wang-Quing, Huguenot, Florent, Inguimbert, Nicolas, Bouaziz, Serge, Vidal, Michel, Broutin, Isabelle, Lascombe, Marie, Permyakov, Eugene, Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Chimie Organique, Médicinale et Extractive et Toxicologie Expérimentale (COMETE - UMR 8638), Centre de recherches insulaires et observatoire de l'environnement (CRIOBE), Université de Perpignan Via Domitia (UPVD)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Pharmacochimie Moléculaire et Cellulaire (PMC - UMR_S 648), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Böttger, Sonja, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Synthèse et structure de molécules d'interet pharmacologique (SSMIP), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre des Matériaux des Mines d'Alès (C2MA), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Université Sorbonne Paris Cité (USPC), Laboratoire de Chimie des Biomolécules et de l'Environnement (LCBE), Université Montpellier 1 (UM1)-Université de Perpignan Via Domitia (UPVD), Unité de Pharmacologie Chimique et Génétique (UPCG - UMR_S 640/UMR 8151), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)

Subjects
0301 basic medicine, Vascular Endothelial Growth Factor A, Dimer, lcsh:Medicine, Plasma protein binding, 01 natural sciences, Physical Chemistry, chemistry.chemical_compound, Chemical Precipitation, Receptor, lcsh:Science, Multidisciplinary, Crystallography, Chemistry, MESH: Protein Multimerization, Physics, Chemical Reactions, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Condensed Matter Physics, Molecular Docking Simulation, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Zinc, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Biochemistry, Physical Sciences, Crystal Structure, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Crystallization, Dimerization, Binding domain, Protein Binding, Research Article, Chemical Elements, Cadmium, Cations, Divalent, Materials by Structure, Chemical physics, Materials Science, Context (language use), Crystals, 03 medical and health sciences, Cations, MESH: Cations, Divalent, Enzyme-linked receptor, Extracellular, MESH: Molecular Docking Simulation, Humans, Solid State Physics, MESH: Protein Binding, Binding site, Ions, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Binding Sites, Vascular Endothelial Growth Factor Receptor-1, MESH: Humans, MESH: Vascular Endothelial Growth Factor Receptor-1, 010405 organic chemistry, MESH: Vascular Endothelial Growth Factor A, lcsh:R, Dimers (Chemical physics), 0104 chemical sciences, 030104 developmental biology, Chemical Properties, MESH: Binding Sites, Biophysics, lcsh:Q, Protein Multimerization
Abstract

International audience; Angiogenesis is tightly regulated through the binding of vascular endothelial growth factors (VEGFs) to their receptors (VEGFRs). In this context, we showed that human VEGFR1 domain 2 crystallizes in the presence of Zn 2+ , Co 2+ or Cu 2+ as a dimer that forms via metal-ion interactions and interlocked hydrophobic surfaces. SAXS, NMR and size exclusion chromatography analyses confirm the formation of this dimer in solution in the presence of Co 2+ , Cd 2+ or Cu 2+ . Since the metal-induced dimerization masks the VEGFs binding surface, we investigated the ability of metal ions to displace the VEGF-A binding to hVEGFR1: using a competition assay, we evidenced that the metals displaced the VEGF-A binding to hVEGFR1 extracellular domain binding at micromolar level.

Published
2016
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49. Biophysical Studies of the InducedDimerization of Human VEGF Receptor 1Binding Domain by Divalent MetalsCompeting with VEGF-A

Author

Gaucher, Jean-François, Reille-Seroussi, Marie, Gagey-Eilstein, Nathalie, Broussy, Sylvain, Coric, Pascale, Seijo, Bili, Lascombe, Marie-Bernard, Gautier, Benoit, Liu , Wang-Quing, Huguenot, Florent, Inguimbert, Nicolas, Bouaziz, Serge, Vidal, Michel, Broutin, Isabelle, Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Université Paris Descartes - Paris 5 (UPD5) - Centre National de la Recherche Scientifique (CNRS), Chimie Organique, Médicinale et Extractive et Toxicologie Expérimentale (COMETE - UMR 8638), Centre de recherches insulaires et observatoire de l'environnement (CRIOBE), Université de Perpignan Via Domitia (UPVD) - École pratique des hautes études (EPHE) - Centre National de la Recherche Scientifique (CNRS), Pharmacochimie Moléculaire et Cellulaire (PMC - UMR_S 648), and Centre National de la Recherche Scientifique (CNRS) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris Descartes - Paris 5 (UPD5)

Subjects
[SDV.IB] Life Sciences [q-bio]/Bioengineering, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences
Abstract

International audience; Angiogenesis is tightly regulated through the binding of vascular endothelial growth factors(VEGFs) to their receptors (VEGFRs). In this context, we showed that human VEGFR1domain 2 crystallizes in the presence of Zn 2+ , Co 2+ or Cu 2+ as a dimer that forms via metal-ion interactions and interlocked hydrophobic surfaces. SAXS, NMR and size exclusion chro-matography analyses confirm the formation of this dimer in solution in the presence of Co 2+ ,Cd 2+ or Cu 2+ . Since the metal-induced dimerization masks the VEGFs binding surface, weinvestigated the ability of metal ions to displace the VEGF-A binding to hVEGFR1: using acompetition assay, we evidenced that the metals displaced the VEGF-A binding tohVEGFR1 extracellular domain binding at micromolar level.

Published
2016
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50. Emerging From the Unknown: Structural and Functional Features of Agnoprotein of Polyomaviruses

Author

Saribas, A Sami, Coric, Pascale, Hamazaspyan, Anahit, Davis, William, Axman, Rachel, White, Martyn, Abou-Gharbia, Magid, Childers, Wayne, Condra, Jon, Bouaziz, Serge, Safak, Mahmut, Saribas, A. Sami, Axman, Rachael, Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Unité de Pharmacologie Chimique et Génétique (UPCG - UMR_S 640/UMR 8151), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], MESH: Humans, viruses, MESH: Polyomavirus, MESH: Polyomavirus Infections, MESH: JC Virus, MESH: Animals, MESH: Transcription Factors, MESH: Viral Proteins, MESH: Viral Regulatory and Accessory Proteins
Abstract

International audience; Agnoprotein is an important regulatory protein of polyomaviruses, including JCV, BKV, and SV40. In the absence of its expression, these viruses are unable to sustain their productive life cycle. It is a highly basic phosphoprotein that localizes mostly to the perinuclear area of infected cells, although a small amount of the protein is also found in nucleus. Much has been learned about the structure and function of this important regulatory protein in recent years. It forms highly stable dimers/oligomers in vitro and in vivo through its Leu/Ile/Phe-rich domain. Structural NMR studies revealed that this domain adopts an alpha-helix conformation and plays a critical role in the stability of the protein. It associates with cellular proteins, including YB-1, p53, Ku70, FEZ1, HP1α, PP2A, AP-3, PCNA, and α-SNAP; and viral proteins, including small t antigen, large T antigen, HIV-1 Tat, and JCV VP1; and significantly contributes the viral transcription and replication. This review summarizes the recent advances in the structural and functional properties of this important regulatory protein. J. Cell. Physiol. 231: 2115-2127, 2016. © 2016 Wiley Periodicals, Inc.

Published
2016
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