title: Crystal structure of human vinculin.
abstract: Alterations in the actin cytoskeleton following the formation of cell-matrix and cell-cell junctions are orchestrated by vinculin. Vinculin associates with a large number of cytoskeletal and signaling proteins, and this flexibility is thought to contribute to rapid dissociation and reassociations of adhesion complexes. Intramolecular interactions between vinculin's head (Vh) and tail (Vt) domains limit access of its binding sites for other adhesion proteins. While the crystal structures of the Vh and Vt domains are known, these domains represent less than half of the entire protein and are separated by a large central region of unknown structure and function. Here we report the crystal structure of human full-length vinculin to 2.85 A resolution. In its resting state, vinculin is a loosely packed collection of alpha-helical bundles held together by Vh-Vt interactions. The three new well ordered alpha-helical bundle domains are similar in their structure to either Vh (Vh2 and Vh3) or to Vt (Vt2) and their loose packing provides the necessary flexibility that allows vinculin to interact with its various protein partners at sites of cell adhesion.
authors.affiliation: Department of Hematology-Oncology, St. Jude Children's Research Hospital, 332 N. Lauderdale Street, Memphis, TN 38105, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Borgon
authors.forename: Clemens
authors.initials: C
authors.lastname: Vonrhein
authors.forename: Gerard
authors.initials: G
authors.lastname: Bricogne
authors.forename: Philippe R J
authors.initials: PR
authors.lastname: Bois
authors.forename: Tina
authors.initials: T
authors.lastname: Izard
mesh_terms: D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion; D002645:Chickens; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016596:Vinculin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D016596:Vinculin