Structural basis of αE-catenin-F-actin catch bond behavior

Cell-cell and cell-matrix junctions transmit mechanical forces during tissue morphogenesis and homeostasis. -Catenin links cell-cell adhesion complexes to the actin cytoskeleton, and mechanical load strengthens its binding to F-actin in a direction-sensitive manner. This so-called catch bond behavior is described by a model in which force promotes a transition between weak and strong actin-bound states. We describe the cryo-electron microscopy structure of the F-actin-bound E-catenin actin-binding domain, which in solution forms a 5-helix bundle. Upon binding to actin, the first helix of the bundle dissociates and the remaining four helices and connecting loops rearrange to form the interface with actin. Deletion of the N-terminal helix produces strong actin binding in the absence of force. Our analysis explains how mechanical force applied to E-catenin or its homolog vinculin favors the strongly bound state, and the dependence of catch bond strength on the direction of applied force.