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

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