6CV7

Mouse Protocadherin-15 Extracellular Cadherin Domains 1 through 3

6CV7 の概要

• エントリーDOI: 10.2210/pdb6cv7/pdb
• 分子名称: Protocadherin-15, CALCIUM ION, 1,2-ETHANEDIOL, ... (6 entities in total)
• 機能のキーワード: cadherin, hair cells, hearing, dimer, cell adhesion, signaling protein
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 44887.96

構造登録者

Dionne, G.,Shapiro, L. (登録日: 2018-03-27, 公開日: 2018-08-01, 最終更新日: 2024-11-20)

主引用文献

Dionne, G.,Qiu, X.,Rapp, M.,Liang, X.,Zhao, B.,Peng, G.,Katsamba, P.S.,Ahlsen, G.,Rubinstein, R.,Potter, C.S.,Carragher, B.,Honig, B.,Muller, U.,Shapiro, L.
Mechanotransduction by PCDH15 Relies on a Novel cis-Dimeric Architecture.
Neuron, 99:480-492.e5, 2018

PubMed Abstract: The tip link, a filament formed by protocadherin 15 (PCDH15) and cadherin 23, conveys mechanical force from sound waves and head movement to open hair-cell mechanotransduction channels. Tip-link cadherins are thought to have acquired structural features critical for their role in mechanotransduction. Here, we biophysically and structurally characterize the unusual cis-homodimeric architecture of PCDH15. We show that PCDH15 molecules form double-helical assemblies through cis-dimerization interfaces in the extracellular cadherin EC2-EC3 domain region and in a unique membrane-proximal domain. Electron microscopy studies visualize the cis-dimeric PCDH15 assembly and reveal the PCDH15 extracellular domain as a parallel double helix with cis cross-bridges at the two locations we defined. The helical configuration suggests the potential for elasticity through helix winding and unwinding. Functional studies in hair cells show that mutations that perturb PCDH15 dimerization contacts affect mechanotransduction. Together, these data reveal the cis-dimeric architecture of PCDH15 and show that dimerization is critical for sensing mechanical stimuli.

PubMed: 30057206
DOI: 10.1016/j.neuron.2018.07.006

実験手法

X-RAY DIFFRACTION (1.692 Å)