A Partial Calcium-Free Linker Confers Flexibility to Inner-Ear Protocadherin-15.

ABSTRACT: Tip links of the inner ear are protein filaments essential for hearing and balance. Two atypical cadherins, cadherin-23 and protocadherin-15, interact in a Ca²⁺-dependent manner to form tip links. The largely unknown structure and mechanics of these proteins are integral to understanding how tip links pull on ion channels to initiate sensory perception. Protocadherin-15 has 11 extracellular cadherin (EC) repeats. Its EC3-4 linker lacks several of the canonical Ca²⁺-binding residues, and contains an aspartate-to-alanine polymorphism (D414A) under positive selection in East Asian populations. We present structures of protocadherin-15 EC3-5 featuring two Ca²⁺-binding linker regions: canonical EC4-5 linker binding three Ca²⁺ ions, and non-canonical E

SUBMITTER: Powers RE 

PROVIDER: S-EPMC5363953 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature