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Start Over Author "Martin Floor" Topic 030104 developmental biology
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1. The energy cost of polypeptide knot formation and its folding consequences

Author

Martin Floor, Carlos Bustamante, Christian A. M. Wilson, Juan Sotelo-Campos, Andrés Bustamante, Mauricio Baez, and Daniel G. Guerra

Subjects
0301 basic medicine, Models, Molecular, polypeptide, Protein Folding, Protein Denaturation, Bacteriophages/metabolism, Optical Tweezers, Protein Conformation, purl.org/pe-repo/ocde/ford#1.03.00 [https], General Physics and Astronomy, Polypeptide chain, Protein stability, Protein structure, bacteriophage, genetics, Bacteriophages, lcsh:Science, energy efficiency, Quantitative Biology::Biomolecules, Multidisciplinary, Chemistry, Quantitative Biology::Molecular Networks, food and beverages, peptide, energy cost, surgical procedures, operative, Optical tweezers, Chemical physics, Thermodynamics, Protein folding, Monte Carlo Method, viral protein, polymer, Science, purl.org/pe-repo/ocde/ford#1.06.03 [https], Nanotechnology, protein localization, chemistry, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Viral Proteins, Knot (unit), stomatognathic system, Viral Proteins/chemistry/genetics, Author Correction, Trefoil knot, General Chemistry, Mathematics::Geometric Topology, 030104 developmental biology, kinetics, Energy cost, Lotus, purl.org/pe-repo/ocde/ford#1.04.00 [https], Monte Carlo analysis, lcsh:Q, molecular model, entropy, metabolism
Abstract

Knots are natural topologies of chains. Yet, little is known about spontaneous knot formation in a polypeptide chain—an event that can potentially impair its folding—and about the effect of a knot on the stability and folding kinetics of a protein. Here we used optical tweezers to show that the free energy cost to form a trefoil knot in the denatured state of a polypeptide chain of 120 residues is 5.8 ± 1 kcal mol−1. Monte Carlo dynamics of random chains predict this value, indicating that the free energy cost of knot formation is of entropic origin. This cost is predicted to remain above 3 kcal mol−1 for denatured proteins as large as 900 residues. Therefore, we conclude that naturally knotted proteins cannot attain their knot randomly in the unfolded state but must pay the cost of knotting through contacts along their folding landscape., The effect of knots on protein stability and folding kinetics is not well understood. Here the authors combine optical tweezer experiments and calculations to experimentally determine the energy cost for knot formation, which indicates that knotted proteins evolved specific folding pathways because knot formation in unfolded chains is unfavorable.

Published
2017
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2. Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

Author

Fritz G. Rathjen, Timothy D. Calamaras, Hong Wang, Motofumi Kumazoe, Sarah Helena Nies, Jerid W. Robinson, Andreas Friebe, Balázs Tamás Németh, Michel Negrerie, Kjetil W. Andressen, Clara D. Ledsky, Sivakanan Loganathan, Kerstin Jurk, Barbara Voussen, Julia Gorelik, Mi Kyung Chang, Johannes-Peter Stasch, Friederike Cuello, Nicholas C. Blixt, S. A. Dames, Nazareno Paolocci, Gzona Bajraktari, Katherine C. Hall, Markus Waldeck-Weiermair, Marcel A. Krüger, Antonius C.F. Gorren, Donté A. Stevens, Daniel Bloch, Deborah M. Dickey, Maria Hernandez-Valladares, Lan Zhao, Alex Vincent, Jenna Scotcher, Andrzej Weichsel, Tamás Radovits, Jeremy Richman, Sophie Schobesberger, Stavros Topouzis, Regine Mühlfriedel, Dennis Busse, Reiner Frey, Sean P. Parsons, René P. Zahedi, Evanthia Mergia, Mathias W. Seeliger, Angela McLaughlin, Sylvia Nikkho, Fernando Ferreira Costa, Pavel Jansa, Ornella Manfra, Wilson A. Ferreira, Inmaculada Silos-Santiago, B. Selin Kenet, Marc Humbert, Garyfalia Makrynitsa, Katja Stehfest, Lise Román Moltzau, Shiliang Li, Chris Sarko, Lincoln R. Potter, Yusu Gu, Scott A. Waldman, Nicole Eichert, David Kilpatrick, Roland Malli, Jun Hino, Robert Solinga, Banumathi Sankaran, William R. Montfort, Alexander Kollau, Julia Davydova, Andriana Stamopoulou, Olena Rudyk, Johanna Weiss, Kenji Kangawa, Arno Fritsch, Meinrad Gawaz, Peter Sandner, Robert M. Blanton, Friedrich Grimminger, Laurinda Jaffe, Atsuko Okamoto, Elke Butt, Stefanie Peters, Christine E. Gee, Ronald J. Holewinski, Zhi Cheng Jing, Andrea Gerling, Mika Takai, Alexander Froese, Hiroshi Hosoda, Mara Goetz, Yasutake Tanaka, Ioannis I. Alexandropoulos, Amie J Moyes, Hyazinth Dobrowinski, Michael J. Shipston, Ulrike Scheib, Stefan W. Hell, Oleksandra Prysyazhna, Lukas Rüttiger, Dieter Groneberg, Vu Thao-Vi Dao, Ulrich Walter, Hariharan Subramanian, Roger Flores-Costa, Richard C. Page, Joerg Reinders, Huaqun Zhang, Dianna M. Milewicz, Martin Thunemann, Albert T. Profy, Chieri Takeuchi, Andrew B. Tobin, Darren E. Casteel, Sarah Jacobson, Philip Eaton, Cor de Witt, Nadine Mauro, Mark Aronovitz, Sevil Korkmaz-Icöz, Barbara Wilhelm, Angelos Vachaviolos, Kim Tang, Axel Gödecke, Christian Meier, Carine M. Boustany, Daniel P. Zimmer, Bernd J. Pichler, Adrian J. Hobbs, Marianne Bjørnerem, Wolfgang F. Graier, Selene J. Sollie, Jenny Tobin, Jürgen Burhenne, Meinoshin Okumura, Nancy D. Dalton, Matthias Karck, Ernst-Martin Füchtbauer, Karoline Dröbner, Kristen M. Kokkonen, Flavia Menezes, Heribert Schunkert, Kirk L. Peterson, Ying-Ju Sung, Georgios A. Spyroulias, Olga N. Petrova, Frank Eitner, Mark G. Currie, Choel Kim, Ulrike Zimmermann, Steven S. Pullen, Shunhui Zhuang, Camila B. Almeida, Sylvie Bernier, M. Wittwer, Steffen Wolter, Stylianos Michalakis, Ralf Kühn, Sara S. O. Saad, Catherine Mansfield, Joon Jung, Jennifer E. Van Eyk, Navin K. Kapur, Renate B. Pilz, David Langleben, Diane Wong, Sylvie G. Bernier, Leia C. Shuhaibar, Heinz G. Körschen, César Ibarra-Alvarado, Courtney Shea, Ryan M. Fryer, Corina Russwurm, Gilbert W. Kim, Gerald Wölkart, Marius M. Hoeper, Astrid Weiss, Harald F. Langer, Ibrahim J. Domian, Lars I. Leichert, Bernd Wissinger, Paul Allan Renhowe, Richard H. Karas, Masayuki Sasaki, Finn Olav Levy, Cor de Wit, Sonia Donzelli, Michael Russwurm, Eberhart Zrenner, Reshma S. Baliga, Holly Clifford, Jonathan C. Schisler, Cheng-Yu Chen, Nicola Conran, Jens Schlossmann, Vikas Kapil, Pablo Colorado, Boris Tchernychev, Isabelle Lamarre, Katrin Reimann, Francheska Colon-Gonzalez, Ralph T. Schermuly, Hans-Ulrich Häring, Vineet Agrawal, Peter Germano, Bernd Mayer, Katharina Beck, Moritz Lehners, Sara Vandenwijngaert, Fabíola Z. Mónica, Pavel I. Nedvetsky, Kimberly Kafadar Long, Silja Meier, Paul A. Corris, Takeshi Tokudome, Shatanik Mukherjee, Joseph R. Burgoyne, Martin Deile, Jan Giesen, Ferid Murad, G. Todd Milne, Shinpei Kawaoka, Koichi Miura, Jessica A. Wales, David A. Kass, Doris Koesling, Hongxing Chen, Frode S. Berven, Jeong Joo Kim, Friedrich W. Herberg, Kristin Hartmann, Martin Biel, Raymond L. Benza, Monte S. Willis, Daniela Bertinetti, Jaime L. Masferrer, Stefan Z. Lutz, Guang-Rong Wang, Peter Ruth, Viacheslav O. Nikolaev, Tobias Peters, Karl Ulrich Bartz-Schmidt, Arnab Ghosh, Lai Wen, Mai Kadomatsu, Sandy M. Chu, Yutaka Suzuki, Marcus Olbrich, Yigao Huang, Tobias Bauch, Thorsten Kessler, Amrita Ahluwalia, Robert Feil, Daniel Richards, Hu Sheng Qian, M Currie, Christopher Newton-Cheh, V. Kaila, Liying Qin, Peter Hegemann, Peter Wright, G-Yoon Jamie Im, Hirofumi Tachibana, Kjestine Schmidt, Pamela L. Brito, Alisa Kamynina, James C. Campbell, Adam E. Snook, Fabian Schwiering, Martin Floor, Jordi Villà-Freixa, Jana Wobst, Alexandre Dumoulin, Ali R. Banijamali, Csaba Mátyás, Harald H.H.W. Schmidt, Susanne Kohl, Mark J. Ranek, Manuela Zaccolo, Robert Lukowski, Robert Naeije, Peter P. Rainer, Stephan Rosenkranz, Emmanuel S. Buys, Simone Romoli, Andreas Papapetropoulos, Kim C. Mansky, James Wakefield, Kálmán Benke, Takashi Nojiri, Aikaterini I. Argyriou, Dongjian Hu, Glenn A. Reinhart, Cornelia Virus, Marius Ueffing, Marlies Knipper, Gerhard Hannig, Kanako Takamatsu, Athanassios Giannis, Miki Arai, Stepan Gambaryan, James E. Sheppeck, Mathew M. Mannion, S. Bruce King, Henriette Andresen, Min Zhang, Jan D. Huizinga, Jeanette Erdmann, Matthias Broser, Astrid Schrammel, Dante J. Merlino, Hossein Ardeschir Ghofrani, Gaia Calamera, Obiajulu Agha, Kathleen A Lincoln, Gerburg K. Schwaerzer, Gordon L. Warren, Andrea Neubauer, Claire Poulet, Nicoletta C. Surdo, Attila Oláh, Damian Brockschnieder, Emrah Eroglu, Carla Fernanda Franco Penteado, Walter E. Haefeli, Mihály Ruppert, Ekkehard Grünig, Konstantina Stathopoulou, Elena Walter, Gérald Simonneau, Béla Merkely, Andreas Güldner, J Keppler, Katharina Frank, Renee Sarno, Sandra Frankenreiter, Sian E. Harding, Dorit Möhrle, Paul C. Harrison, Péter Hegedűs, Hyun-Soon Geisler, James R. Klinger, Markus Wolters, Philipp Henning, Jieru E. Lin, Erik S. Blomain, Alessandro Cataliotti, Ditta Zobor, Mikiya Miyazato, Marissa Opelt, Christian Schön, John Fassett, Yue Dai, Q. Luo, Thomas G. Oertner, Linda Breci, Robert A Baumgartner, Shun Hiroi, Ping Zhang, Albert Smolenski, Paul S. Frenette, Mahmood M. Alam, Jeremy R. Egbert, Dennis J. Stuehr, Eugen Franz, Hanan Chweih, Dong I. Lee, Nadja I. Bork, Guang Liu, Hannes Schmidt, Ka Bian, Annemarie Aue, Christian Dees, Edward Seto, Manuela Harloff, Michael Paolillo Hannes Schmidt, Susanne Feil, Susanne Krasemann, Andrea Hembre Ulsund, Marina Bantzi, Laurinda A. Jaffe, Luis Agulló, Dominik M. Fischer, Wendy Baur, Kjetil Wessel Andressen, Saurav Misra, Gábor Szabó, and Oliver Pagel

Subjects
0301 basic medicine, Pharmacology, 03 medical and health sciences, 030104 developmental biology, business.industry, Pharmacology toxicology, MEDLINE, Medicine, Pharmacology (medical), business
Published
2017
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3. Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif

Author

Jorge Carrillo, F.-Xabier Contreras, Eneritz Bilbao, Nuria Izquierdo-Useros, María Luisa Rodríguez de la Concepción, Bonaventura Clotet, Elisabet García, Luis M. Molinos-Albert, Silvia Marfil, Maier Lorizate, Julià Blanco, Pere J. Cardona, Jordi Villà-Freixa, Javier Martinez-Picado, Jon Ander Nieto-Garai, Luis Agulló, Cristina Vilaplana, Martin Floor, Universitat de Vic - Universitat Central de Catalunya. Departament de Biociències, and Universitat de Vic - Universitat Central de Catalunya. Càtedra de la Sida i Malalties Relacionades

Subjects
0301 basic medicine, Membrane lipids, Monophosphoryl Lipid A, Immunoglobulins, Antígens, Bioinformatics, Epitope, Article, 03 medical and health sciences, chemistry.chemical_compound, Epitopes, Membrane Lipids, Mice, 0302 clinical medicine, Immunogenicity, Vaccine, Antigen, Tetanus Toxoid, VIH (Virus), Animals, Immunodeficiency, Antigens, POPC, Inmunoglobulinas, Immunodeficiència, Inmunodeficiencia, Liposome, Multidisciplinary, Immunogenicity, Toxoid, Antígenos, Sida -- Tractament, Molecular biology, Lipids, HIV Envelope Protein gp41, Infecciones por VIH, Mice, Inbred C57BL, 030104 developmental biology, chemistry, Lípids, Lípidos, Female, Infeccions per VIH, lipids (amino acids, peptides, and proteins), Peptides, Immunoglobulines, 030217 neurology & neurosurgery, HIV infections
Abstract

Altres ajuts: Programa HIVACAT, programa CERCA (Generalitat de Catalunya), Red Temática Cooperativa de Investigación en SIDA (RD12/0017/0002)), Govern Basc (IT838-13), Spanish Supercomputing Network (grant numbers BCV-2015-2-0009 and BCV-2016-2-0005) The HIV-1 gp41 Membrane Proximal External Region (MPER) is recognized by broadly neutralizing antibodies and represents a promising vaccine target. However, MPER immunogenicity and antibody activity are influenced by membrane lipids. To evaluate lipid modulation of MPER immunogenicity, we generated a 1-Palmitoyl-2-oleoylphosphatidylcholine (POPC)-based proteoliposome collection containing combinations of phosphatidylserine (PS), GM3 ganglioside, holesterol (CHOL), sphingomyelin (SM) and the TLR4 agonist monophosphoryl lipid A (MPLA). A recombinant gp41-derived miniprotein (gp41-MinTT) exposing the MPER and a tetanus toxoid (TT) peptide that favors MHC-II presentation, was successfully incorporated into lipid mixtures (>85%). Immunization of mice with soluble gp41-MinTT exclusively induced responses against the TT peptide, while POPC proteoliposomes generated potent anti-gp41 IgG responses using lower protein doses. The combined addition of PS and GM3 or CHOL/SM to POPC liposomes greatly increased gp41 immunogenicity, which was further enhanced by the addition of MPLA. Responses generated by all proteoliposomes targeted the N-terminal moiety of MPER overlapping the 2F5 neutralizing epitope. Our data show that lipids impact both, the epitope targeted and the magnitude of the response to membrane-dependent antigens, helping to improve MPER-based lipid carriers. Moreover, the identification of immunodominant epitopes allows for the redesign of immunogens targeting MPER neutralizing determinants.

Published
2017

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