2WBX

Crystal structure of mouse cadherin-23 EC1

Summary for 2WBX

• Entry DOI: 10.2210/pdb2wbx/pdb
• Related: 2WCP
• Descriptor: CADHERIN-23, CALCIUM ION (3 entities in total)
• Functional Keywords: cell adhesion, hearing, deafness
• Biological source: MUS MUSCULUS (MOUSE)
• Cellular location: Cell membrane; Single-pass type I membrane protein (By similarity): Q99PF4
• Total number of polymer chains: 1
• Total formula weight: 11588.90

Authors

Sotomayor, M.,Weihofen, W.,Gaudet, R.,Corey, D.P. (deposition date: 2009-03-05, release date: 2010-04-21, Last modification date: 2023-12-13)

Primary citation

Sotomayor, M.,Weihofen, W.,Gaudet, R.,Corey, D.P.
Structural Determinants of Cadherin-23 Function in Hearing and Deafness.
Neuron, 66:85-, 2010

PubMed Abstract: The hair-cell tip link, a fine filament directly conveying force to mechanosensitive transduction channels, is composed of two proteins, protocadherin-15 and cadherin-23, whose mutation causes deafness. However, their molecular structure, elasticity, and deafness-related structural defects are unknown. We present crystal structures of the first and second extracellular cadherin repeats of cadherin-23. Overall, structures show typical cadherin folds, but reveal an elongated N terminus that precludes classical cadherin interactions and contributes to an N-terminal Ca(2+)-binding site. The deafness mutation D101G, in the linker region between the repeats, causes a slight bend between repeats and decreases Ca(2+) affinity. Molecular dynamics simulations suggest that cadherin-23 repeats are stiff and that either removing Ca(2+) or mutating Ca(2+)-binding residues reduces rigidity and unfolding strength. The structures define an uncharacterized cadherin family and, with simulations, suggest mechanisms underlying inherited deafness and how cadherin-23 may bind with itself and with protocadherin-15 to form the tip link.

PubMed: 20399731
DOI: 10.1016/J.NEURON.2010.03.028

Experimental method

X-RAY DIFFRACTION (1.5 Å)