5KJ4

Crystal Structure of Mouse Protocadherin-15 EC9-10

Summary for 5KJ4

• Entry DOI: 10.2210/pdb5kj4/pdb
• Descriptor: Protocadherin-15, CALCIUM ION (3 entities in total)
• Functional Keywords: hearing, mechanotransduction, adhesion, calcium-binding protein
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 4
• Total formula weight: 104365.58

Authors

Araya-Secchi, R.,Sotomayor, M. (deposition date: 2016-06-17, release date: 2016-11-23, Last modification date: 2023-09-27)

Primary citation

Araya-Secchi, R.,Neel, B.L.,Sotomayor, M.
An elastic element in the protocadherin-15 tip link of the inner ear.
Nat Commun, 7:13458-13458, 2016

PubMed 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.

PubMed: 27857071
DOI: 10.1038/ncomms13458

Experimental method

X-RAY DIFFRACTION (3.35 Å)