PDBsum entry 5wjm

Cell adhesion

PDB id: 5wjm

Contents

Protein chain

216 a.a.

Ligands

MPD ×2

Metals

_CA ×6

__K

Waters ×23

PDB id:

5wjm

Name:

Cell adhesion

Title:

Crystal structure of mouse cadherin-23 ec17-18

Structure:

Cadherin-23. Chain: a. Fragment: residues 1739-1954. Synonym: otocadherin. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: cdh23. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Resolution:

2.90Å R-factor: 0.203 R-free: 0.266

Authors:

P.De-La-Torre,M.Sotomayor

Key ref:

A.Jaiganesh et al. (2018). Zooming in on Cadherin-23: Structural Diversity and Potential Mechanisms of Inherited Deafness. Structure, 26, 1210. PubMed id: 30033219 DOI: 10.1016/j.str.2018.06.003

Date:

23-Jul-17 Release date: 04-Jul-18

Protein chain

Q99PF4  (CAD23_MOUSE) -  Cadherin-23 from Mus musculus

Seq: 3354 a.a.

Struc: 216 a.a.

DOI no: 10.1016/j.str.2018.06.003

Structure 26:1210 (2018)

PubMed id: 30033219

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

A.Jaiganesh, P.De-la-Torre, A.A.Patel, D.J.Termine, F.Velez-Cortes, C.Chen, M.Sotomayor.

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 structure. Complementary experiments show deafness mutations' effects on stability and affinity for Ca²⁺. 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.