Conformational switch of harmonin, a submembrane scaffold protein of the hair cell mechanoelectrical transduction machinery

Autor: Bahloul, Amel, Pepermans, Elise, Raynal, Bertrand, Wolff, Nicolas, Cordier, Florence, England, Patrick, Nouaille, Sylvie, Baron, Bruno, El‐Amraoui, Aziz, Hardelin, Jean‐Pierre, Durand, Dominique, Petit, Christine
Přispěvatelé: Chaire Génétique et physiologie cellulaire, Collège de France (CdF (institution)), Biophysique Moléculaire (Plate-forme), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Résonance Magnétique Nucléaire des Biomolécules, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), This work was supported by Institut Pasteur PTR program No.483, by the European Union Seventh Framework Programme under the grant agreement HEALTH‐F2‐2010‐242013 (TREATRUSH), the European Commission (Hairbundle ERC‐2011‐ADG_294570), by Agence Nationale de la Recherche (ANR) within the framework of the Investissements d'Avenir program (ANR‐15‐RHUS‐0001), Laboratoire d'excellence (LabEx) Lifesenses (ANR‐10‐LABX‐65), ANR‐11‐IDEX‐0004‐02, ANR‐11‐BSV5‐0011, and grants from Fondation Agir pour l'Audition, the BNP Paribas Foundation, the FAUN Stiftung, the LHW‐Stiftung and Mrs. Errera Hoechstetter, We thank Sébastien Brulé from the biophysical platform for technical support, We thank the staff of the SWING beamline for help during the SAXS measurements., ANR-15-RHUS-0001,LIGHT4DEAF,ECLAIRER LA SURDITÉ : UNE APPROCHE HOLISTIQUE DU SYNDROME D'USHER(2015), ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), ANR-11-BSV5-0011,EARMEC,Propriétés mécaniques, actives et passives, de la touffe ciliaire des cellules mécano-sensorielles ciliées le long de l'axe tonotopique de la cochlée des mammifères.(2011), European Project: 242013,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,TREATRUSH(2010), European Project: 294570,EC:FP7:ERC,ERC-2011-ADG_20110310,HAIRBUNDLE(2012), Collège de France - Chaire Génétique et physiologie cellulaire, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2017
Předmět:
MESH: Signal Transduction
Protein Conformation
PDZ domain
Cell Cycle Proteins
conformation switch
MESH: Cadherins
MESH: Circular Dichroism
MESH: Protein Conformation
Protein Domains
X-Ray Diffraction
Structural Biology
Scattering
Small Angle
MESH: Nuclear Magnetic Resonance
Biomolecular
Research Letter
otorhinolaryngologic diseases
Humans
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biochemistry [q-bio.BM]
Nuclear Magnetic Resonance
Biomolecular
Biology
MESH: Scattering
Small Angle
Adaptor Proteins
Signal Transducing
MESH: Adaptor Proteins
Signal Transducing
MESH: Humans
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Structural Biology [q-bio.BM]
Circular Dichroism
Physics
MESH: X-Ray Diffraction
Surface Plasmon Resonance
Cadherins
Research Letters
MESH: Surface Plasmon Resonance
[SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biophysics
Cytoskeletal Proteins
Chemistry
HEK293 Cells
MESH: HEK293 Cells
MESH: Protein Domains
Human medicine
Usher syndrome
Signal Transduction
Zdroj: FEBS Letters
FEBS Letters, Wiley, 2017, 591 (15), pp.2299-2310. ⟨10.1002/1873-3468.12729⟩
FEBS Letters, 2017, 591 (15), pp.2299-2310. ⟨10.1002/1873-3468.12729⟩
FEBS LETTERS
Febs Letters
ISSN: 0014-5793
1873-3468
Popis: International audience; Mutations in the gene encoding harmonin, a multi-PDZ domain-containing submembrane protein, cause Usher syndrome type 1 (congenital deafness and balance disorder, and early-onset sight loss). The structure of the protein and biological activities of its three different classes of splice isoforms (a, b, and c) remain poorly understood. Combining biochemical and biophysical analyses , we show that harmonin-a1 can switch between open and closed conforma-tions through intramolecular binding of its C-terminal PDZ-binding motif to its N-terminal supramodule NTD-PDZ1 and through a flexible PDZ2-PDZ3 linker. This conformational switch presumably extends to most harmonin iso-forms, and it is expected to have an impact on the interaction with some binding partners, as shown here for cadherin-related 23, another component of the hair cell mechanoelectrical transduction machinery.
Databáze: OpenAIRE
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