An elastic element in the protocadherin-15 tip link of the inner ear

Raul Araya-Secchi, Brandon L. Neel and Marcos Sotomayor ()
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Raul Araya-Secchi: The Ohio State University
Brandon L. Neel: The Ohio State University
Marcos Sotomayor: The Ohio State University

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract Tip link filaments convey force and gate inner-ear hair-cell transduction channels to mediate perception of sound and head movements. Cadherin-23 and protocadherin-15 form tip links through a calcium-dependent interaction of their extracellular domains made of multiple extracellular cadherin (EC) repeats. These repeats are structurally similar, but not identical in sequence, often featuring linkers with conserved calcium-binding sites that confer mechanical strength to them. Here we present the X-ray crystal structures of human protocadherin-15 EC8–EC10 and mouse EC9–EC10, which show an EC8–9 canonical-like calcium-binding linker, and an EC9–10 calcium-free linker that alters the linear arrangement of EC repeats. Molecular dynamics simulations and small-angle X-ray scattering experiments support this non-linear conformation. Simulations also suggest that unbending of EC9–10 confers some elasticity to otherwise rigid tip links. The new structure provides a first view of protocadherin-15’s non-canonical EC linkers and suggests how they may function in inner-ear mechanotransduction, with implications for other cadherins.

Date: 2016
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DOI: 10.1038/ncomms13458

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