Structural plasticity of the HHD 2 domain of whirlin

Autor: Florence Cordier, Nicolas Wolff, Ahmed Haouz, Lucas Chataigner, Florent Delhommel, Frederick Saul
Přispěvatelé: Récepteurs Canaux - Channel Receptors, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Collège doctoral [Sorbonne universités], Sorbonne Université (SU), Bioinformatique structurale - Structural Bioinformatics, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Cristallographie (Plateforme) - Crystallography (Platform), Financial support from the TGIR‐RMN‐THC Fr3050 CNRS for conducting the research is gratefully acknowledged. The authors acknowledge the Conseil Régional d'Ile de France for financial support through the SESAME 2014 NMRCHR program No. 14014526 (800 MHz spectrometer). This work was supported by the Programme Transversal de Recherche from Institut Pasteur (PTR grant no. 483 to NW), the Ministère de l'Enseignement Supérieur et de la Recherche (grant no. 883/2013 to FD), and the Comité Berthe Fouassier – Maladies de l'oeil de la Fondation de France (no. 00071779 to FD)., We acknowledge synchrotrons SOLEIL for provision of synchrotron radiation facilities and we would like to thank the staff of beamlines PROXIMA 1 and SWING for assistance. The authors are grateful to the staff of the Crystallographic platform at Institut Pasteur for robot‐driven crystallization screening. We thank Bertrand Raynal (Biophysics platform, Institut Pasteur) for SAXS expertise and helpful discussions and Amel Bahloul and Christine Petit (Génétique et Physiologie de l'Audition, Institut Pasteur) for helpful discussions., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Collège Doctoral
Rok vydání: 2018
Předmět:
Zdroj: FEBS Journal
FEBS Journal, Wiley, 2018, 285 (20), pp.3738-3752. ⟨10.1111/febs.14614⟩
FEBS Journal, 2018, 285 (20), pp.3738-3752. ⟨10.1111/febs.14614⟩
ISSN: 1742-4658
1742-464X
DOI: 10.1111/febs.14614
Popis: International audience; Whirlin is a protein essential to sensory neurons. Its defects are responsible for nonsyndromic deafness or for the Usher syndrome, a condition associating congenital deafness and progressive blindness. This large multidomain scaffolding protein is expressed in three isoforms with different functions and localizations in stereocilia bundles of hearing hair cells or in the connecting cilia of photoreceptor cells. The HHD2 domain of whirlin is the only domain shared by all isoforms, but its function remains unknown. In this article, we report its crystal structure in two distinct conformations, a monomeric five‐helix bundle, similar to the known structure of other HHD domains, and a three‐helix bundle organized as a swapped dimer. Most of the hydrophobic contacts and electrostatic interactions that maintain the globular monomeric form are conserved at the protomer interface of the dimer. NMR experiments revealed that the five‐helix conformation is predominant in solution, but exhibits increased dynamics on one face encompassing the hinge loops. Using NMR and SAXS, we also show that HHD2 does not interact with its preceding domains. Our findings suggest that structural plasticity might play a role in the function of the HHD2 domain
Databáze: OpenAIRE
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