Dimer asymmetry defines α-catenin interactions

The F-actin-binding cytoskeletal protein a-catenin interacts with beta-catenin-cadherin complexes and stabilizes cell-cell junctions. The beta-catenin-alpha-catenin complex cannot bind F-actin, whereas interactions of alpha-catenin with the cytoskeletal protein vinculin appear to be necessary to stabilize adherens junctions. Here we report the crystal structure of nearly full-length human alpha-catenin at 3.7-angstrom resolution. alpha-catenin forms an asymmetric dimer where the four-helix bundle domains of each subunit engage in distinct intermolecular interactions. This results in a left handshake-like dimer, wherein the two subunits have remarkably different conformations. The crystal structure explains why dimeric alpha-catenin has a higher affinity for F-actin than does monomeric alpha-catenin, why the beta-catenin-alpha-catenin complex does not bind F-actin, how activated vinculin links the cadherin-catenin complex to the cytoskeleton and why a-catenin but not inactive vinculin can bind F-actin.