An Autoinhibited Structure of α-Catenin and Its Implications for Vinculin Recruitment to Adherens Junctions

• DOI: 10.1074/jbc.m113.453928
• Publication Date: 2013-04-16T00:13:21Z
• Authors: Noboru Ishiyama; Nobutoshi Tanaka; Kentaro Abe; Yoo Jeong Yang; Yazan M. Abbas; Masataka Umitsu; Bhushan Nagar; Stephanie A. Bueler; John L. Rubinstein; Masatoshi Takeichi; Mitsuhiko Ikura
• Keywords: 0301 basic medicine; Nerve Tissue Proteins; Adherens Junctions; Crystallography, X-Ray; Models, Biological; Vinculin; Cell Line; Protein Structure, Tertiary; Actin Cytoskeleton; Mice; Structure-Activity Relationship; 03 medical and health sciences; Animals; alpha Catenin

α-Catenin is an actin- and vinculin-binding protein that regulates cell-cell adhesion by interacting with cadherin adhesion receptors through β-catenin, but the mechanisms by which it anchors the cadherin-catenin complex to the actin cytoskeleton at adherens junctions remain unclear. Here we determined crystal structures of αE-catenin in the autoinhibited state and the actin-binding domain of αN-catenin. Together with the small-angle x-ray scattering analysis of full-length αN-catenin, we deduced an elongated multidomain assembly of monomeric α-catenin that structurally and functionally couples the vinculin- and actin-binding mechanisms. Cellular and biochemical studies of αE- and αN-catenins show that αE-catenin recruits vinculin to adherens junctions more effectively than αN-catenin, partly because of its higher affinity for actin filaments. We propose a molecular switch mechanism involving multistate conformational changes of α-catenin. This would be driven by actomyosin-generated tension to dynamically regulate the vinculin-assisted linkage between adherens junctions and the actin cytoskeleton.