5w4t

Publication Abstract from PubMed

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 (Ca(2+)) coordination at the EC linker regions is key for tip-link elasticity and function. There are approximately 116 sites in CDH23 affected by deafness-causing mutations, many of which alter conserved Ca(2+)-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 Ca(2+)-binding motif sequences and unusual secondary structure. Complementary experiments show deafness mutations' effects on stability and affinity for Ca(2+). Additionally, a model of nine contiguous CDH23 EC repeats reveals helicity and potential parallel dimerization faces. Overall, our studies provide detailed structural insight into CDH23 function in mechanotransduction.

Zooming in on Cadherin-23: Structural Diversity and Potential Mechanisms of Inherited Deafness.,Jaiganesh A, De-la-Torre P, Patel AA, Termine DJ, Velez-Cortes F, Chen C, Sotomayor M Structure. 2018 Jun 27. pii: S0969-2126(18)30209-0. doi:, 10.1016/j.str.2018.06.003. PMID:30033219^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.