title: Dimer asymmetry defines α-catenin interactions.
abstract: The F-actin-binding cytoskeletal protein α-catenin interacts with β-catenin-cadherin complexes and stabilizes cell-cell junctions. The β-catenin-α-catenin complex cannot bind F-actin, whereas interactions of α-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 α-catenin at 3.7-Å resolution. α-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 α-catenin has a higher affinity for F-actin than does monomeric α-catenin, why the β-catenin-α-catenin complex does not bind F-actin, how activated vinculin links the cadherin-catenin complex to the cytoskeleton and why α-catenin but not inactive vinculin can bind F-actin.
authors.affiliation: Department of Cancer Biology, Scripps Research Institute, Jupiter, Florida, USA.
authors.forename: Erumbi S
authors.initials: ES
authors.lastname: Rangarajan
authors.forename: Tina
authors.initials: T
authors.lastname: Izard
mesh_terms: D000199:Actins / Q000378:metabolism; D022005:Adherens Junctions / Q000235:genetics / Q000378:metabolism*; D002850:Chromatography, Gel; D018360:Crystallography, X-Ray; D019281:Dimerization; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D015151:Immunoblotting; D008958:Models, Molecular; D011487:Protein Conformation; D016596:Vinculin / Q000378:metabolism*; D014961:X-Ray Diffraction; D051178:alpha Catenin / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D000199:Actins; D051178:alpha Catenin; D016596:Vinculin