9DVA

F-actin binding interface of alpha-E-catenin ABD (cadherin-catenin complex) and afadin

9DVA の概要

• エントリーDOI: 10.2210/pdb9dva/pdb
• EMDBエントリー: 47194
• 分子名称: Actin, alpha skeletal muscle, Catenin alpha-1, Afadin, ... (5 entities in total)
• 機能のキーワード: cytoskeleton, cell adhesion, structural protein
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 438006.02

構造登録者

Gong, R.,Reynolds, M.J.,Alushin, G.M. (登録日: 2024-10-07, 公開日: 2024-10-30)

主引用文献

Gong, R.,Reynolds, M.J.,Sun, X.,Alushin, G.M.
Afadin mediates cadherin-catenin complex clustering on F-actin linked to cooperative binding and filament curvature.
Biorxiv, 2024

PubMed Abstract: The E-cadherin-β-catenin-αE-catenin (cadherin-catenin) complex couples the cytoskeletons of neighboring cells at adherens junctions (AJs) to mediate force transmission across epithelia. Mechanical force and auxiliary binding partners converge to stabilize the cadherin-catenin complex's inherently weak binding to actin filaments (F-actin) through unclear mechanisms. Here we show that afadin's coiled-coil (CC) domain and vinculin synergistically enhance the cadherin-catenin complex's F-actin engagement. The cryo-EM structure of an E-cadherin-β-catenin-αE-catenin-vinculin-afadin-CC supra-complex bound to F-actin reveals that afadin-CC bridges adjacent αE-catenin actin-binding domains along the filament, stabilizing flexible αE-catenin segments implicated in mechanical regulation. These cooperative binding contacts promote the formation of supra-complex clusters along F-actin. Additionally, cryo-EM variability analysis links supra-complex binding along individual F-actin strands to nanoscale filament curvature, a deformation mode associated with cytoskeletal forces. Collectively, this work elucidates a mechanistic framework by which vinculin and afadin tune cadherin-catenin complex-cytoskeleton coupling to support AJ function across varying mechanical regimes.

PubMed: 39415991
DOI: 10.1101/2024.10.08.617332

実験手法

ELECTRON MICROSCOPY (3.1 Å)