2WCP

CRYSTAL STRUCTURE OF MOUSE CADHERIN-23 EC1-2

2WCP の概要

• エントリーDOI: 10.2210/pdb2wcp/pdb
• 関連するPDBエントリー: 2WBX 2WD0
• 分子名称: CADHERIN-23, CALCIUM ION, SODIUM ION, ... (6 entities in total)
• 機能のキーワード: cell adhesion, hearing, deafness
• 由来する生物種: MUS MUSCULUS (MOUSE)
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein (By similarity): Q99PF4
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 24265.28

構造登録者

Sotomayor, M.,Weihofen, W.,Gaudet, R.,Corey, D.P. (登録日: 2009-03-13, 公開日: 2010-04-21, 最終更新日: 2023-12-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.98 Å)