Structural Characterization of Whirlin Reveals an Unexpected and Dynamic Supramodule Conformation of Its PDZ Tandem
| Autor: | Christine Petit, Florent Delhommel, Benjamin Bardiaux, Julia Chamot-Rooke, Michael Nilges, Sébastien Brier, Florence Cordier, Amel Bahloul, Bertrand Raynal, Sylvie Nouaille, Nicolas Wolff, Baptiste Colcombet-Cazenave, Guillaume Bouvier |
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| Přispěvatelé: | ED 515 - Complexité du vivant, Université Pierre et Marie Curie - Paris 6 (UPMC), Résonance Magnétique Nucléaire des Biomolécules, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Bioinformatique structurale - Structural Bioinformatics, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Spectrométrie de Masse structurale et protéomique, Biophysique Moléculaire (Plate-forme), Chaire Génétique et physiologie cellulaire, Collège de France (CdF (institution)), Bioinformatique Structurale, Financial support from TGIR-RMN-THC Fr3050 CNRS for conducting the research is gratefully acknowledged. We acknowledge SOLEIL and ESRF for provision of synchrotron radiation facilities, and we would like to thank the staff of the SWING and BM29 BioSAXS beamlines for assistance during the SAXS measurements. This work was supported by the Program Transversal de Recherche from the Institut Pasteur (PTR grant no. 483 to N.W.), the European Union (FP7-IDEAS-ERC 294809 to M.N.), the Ministère de l’Enseignement Supérieur et de la Recherche (grant no. 883/2013 to F.D), and the Comité Berthe Fouassier – Maladies de l’œil de la Fondation de France (no. 00071779 to F.D)., The authors are grateful to Bradley Worley for careful proofreading of the manuscript and to Muriel Delepierre for useful discussions. We thank Olivier Lequin, Patrick England, and Alain Chaffotte for their technical expertise., European Project: 294809,EC:FP7:ERC,ERC-2011-ADG_20110310,BAYCELLS(2012), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Collège de France - Chaire Génétique et physiologie cellulaire, Wolff, Nicolas, A Bayesian Framework for Cellular Structural Biology - BAYCELLS - - EC:FP7:ERC2012-05-01 - 2017-04-30 - 294809 - VALID |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Protein Conformation
alpha-Helical 0301 basic medicine Scaffold protein Protein Folding MESH: Sequence Homology Amino Acid MESH: PDZ Domains MESH: Nerve Tissue Proteins / genetics Gene Expression PDZ Domains MESH: Amino Acid Sequence MESH: Escherichia coli / genetics 01 natural sciences Mice Transduction (genetics) Structural Biology MESH: Hair Cells Auditory / metabolism MESH: Animals MESH: Molecular Dynamics Simulation MESH: Membrane Proteins / metabolism Cloning Molecular MESH: Peptides / chemistry MESH: Membrane Proteins / genetics Tandem [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Structural Biology [q-bio.BM] SAXS Recombinant Proteins Thermodynamics Stereocilia bundle MESH: Protein Conformation beta-Strand MESH: Escherichia coli / metabolism MESH: Thermodynamics MESH: Hair Cells Auditory / cytology Usher syndrome Protein Binding MESH: Recombinant Proteins / chemistry supramodule MESH: Gene Expression [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry Molecular Biology/Structural Biology [q-bio.BM] MESH: Protein Folding Genetic Vectors PDZ domain MESH: Sequence Alignment Nerve Tissue Proteins MESH: Nerve Tissue Proteins / chemistry Molecular Dynamics Simulation Biology 010402 general chemistry Closed conformation MESH: Membrane Proteins / chemistry Electric signal 03 medical and health sciences NMR spectroscopy Hair Cells Auditory Escherichia coli otorhinolaryngologic diseases Animals MESH: Protein Binding MESH: Cloning Molecular Amino Acid Sequence MESH: Genetic Vectors / chemistry Molecular Biology MESH: Mice MESH: Nerve Tissue Proteins / metabolism MESH: Protein Conformation alpha-Helical MESH: Peptides / chemical synthesis Binding Sites whirlin Sequence Homology Amino Acid Stereocilia Membrane Proteins 0104 chemical sciences Crystallography 030104 developmental biology MESH: Genetic Vectors / metabolism MESH: Binding Sites Biophysics Protein Conformation beta-Strand sense organs MESH: Recombinant Proteins / metabolism Peptides Sequence Alignment MESH: Recombinant Proteins / genetics |
| Zdroj: | Structure Structure, Elsevier (Cell Press), 2017, 25 (11), pp.1645-1656.e5. ⟨10.1016/j.str.2017.08.013⟩ Structure, 2017, 25 (11), pp.1645-1656.e5. ⟨10.1016/j.str.2017.08.013⟩ |
| ISSN: | 0969-2126 |
| DOI: | 10.1016/j.str.2017.08.013⟩ |
| Popis: | International audience; Hearing relies on the transduction of sound-evoked vibrations into electric signals, occurring in the stereocilia bundle of hair cells. The bundle is organized in a staircase pattern formed by rows of packed stereocilia. This architecture is pivotal to transduction and involves a network of scaffolding proteins with hitherto uncharacterized features. Key interactions in this network are mediated by PDZ domains. Here, we describe the architecture of the first two PDZ domains of whirlin, a protein involved in these assemblies and associated with congenital deaf-blindness. C-terminal hairpin extensions of the PDZ domains mediate the transient supramodular assembly, which improves the binding capacity of the first domain. We determined a detailed structural model of the closed conformation of the PDZ tandem and characterized its equilibrium with an ensemble of open conformations. The structural and dynamic behavior of this PDZ tandem provides key insights into the regulatory mechanisms involved in the hearing machinery. |
| Databáze: | OpenAIRE |
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