Zooming in on Cadherin-23: Structural Diversity and Potential Mechanisms of Inherited Deafness.

ABSTRACT: Cadherin-23 (CDH23) is an essential component of hair-cell tip links, fine filaments that mediate inner-ear mechanotransduction. The extracellular domain of CDH23 forms about three-fourths of the tip link with 27 extracellular cadherin (EC) repeats that are structurally similar but not identical to each other. Calcium (Ca²⁺) coordination at the EC linker regions is key for tip-link elasticity and function. There are ∼116 sites in CDH23 affected by deafness-causing mutations, many of which alter conserved Ca²⁺-binding residues. Here we present crystal structures showing 18 CDH23 EC repeats, including the most and least conserved, a fragment carrying disease mutations, and EC repeats with non-canonical Ca²⁺-binding motif sequences and unusual secondary struct

SUBMITTER: Jaiganesh A 

PROVIDER: S-EPMC6375707 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature