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Conformational switch of harmonin, a submembrane scaffold protein of the hair cell mechanoelectrical transduction machinery
Author(s) -
Bahloul Amel,
Pepermans Elise,
Raynal Bertrand,
Wolff Nicolas,
Cordier Florence,
England Patrick,
Nouaille Sylvie,
Baron Bruno,
ElAmraoui Aziz,
Hardelin JeanPierre,
Durand Dominique,
Petit Christine
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12729
Subject(s) - pdz domain , usher syndrome , scaffold protein , gene isoform , microbiology and biotechnology , hek 293 cells , hair cell , transduction (biophysics) , chemistry , signal transduction , biology , biophysics , neuroscience , gene , biochemistry , inner ear , retinitis pigmentosa
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 conformations through intramolecular binding of its C‐terminal PDZ ‐binding motif to its N‐terminal supramodule NTD ‐ PDZ 1 and through a flexible PDZ 2‐ PDZ 3 linker. This conformational switch presumably extends to most harmonin isoforms, 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.