6DV1

Crystal structure of the alpha-E-catenin actin-binding domain

6DV1 の概要

• エントリーDOI: 10.2210/pdb6dv1/pdb
• 分子名称: Catenin alpha-1, BROMIDE ION, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: five-helix bundle, f-actin-binding, mechanosensor, cell adhesion
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 58252.25

構造登録者

Ishiyama, N.,Ikura, M. (登録日: 2018-06-22, 公開日: 2018-12-19, 最終更新日: 2024-03-13)

主引用文献

Ishiyama, N.,Sarpal, R.,Wood, M.N.,Barrick, S.K.,Nishikawa, T.,Hayashi, H.,Kobb, A.B.,Flozak, A.S.,Yemelyanov, A.,Fernandez-Gonzalez, R.,Yonemura, S.,Leckband, D.E.,Gottardi, C.J.,Tepass, U.,Ikura, M.
Force-dependent allostery of the alpha-catenin actin-binding domain controls adherens junction dynamics and functions.
Nat Commun, 9:5121-5121, 2018

PubMed Abstract: α-catenin is a key mechanosensor that forms force-dependent interactions with F-actin, thereby coupling the cadherin-catenin complex to the actin cytoskeleton at adherens junctions (AJs). However, the molecular mechanisms by which α-catenin engages F-actin under tension remained elusive. Here we show that the α1-helix of the α-catenin actin-binding domain (αcat-ABD) is a mechanosensing motif that regulates tension-dependent F-actin binding and bundling. αcat-ABD containing an α1-helix-unfolding mutation (H1) shows enhanced binding to F-actin in vitro. Although full-length α-catenin-H1 can generate epithelial monolayers that resist mechanical disruption, it fails to support normal AJ regulation in vivo. Structural and simulation analyses suggest that α1-helix allosterically controls the actin-binding residue V796 dynamics. Crystal structures of αcat-ABD-H1 homodimer suggest that α-catenin can facilitate actin bundling while it remains bound to E-cadherin. We propose that force-dependent allosteric regulation of αcat-ABD promotes dynamic interactions with F-actin involved in actin bundling, cadherin clustering, and AJ remodeling during tissue morphogenesis.

PubMed: 30504777
DOI: 10.1038/s41467-018-07481-7

実験手法

X-RAY DIFFRACTION (2.2 Å)