title: Structural studies on full-length talin1 reveal a compact auto-inhibited dimer: implications for talin activation.
abstract: Talin is a large adaptor protein that activates integrins and couples them to cytoskeletal actin. Talin contains an N-terminal FERM (band 4.1, ezrin, radixin, moesin) domain (the head) linked to a flexible rod comprised of 13 amphipathic helical bundles (R1-R13) that terminate in a C-terminal helix (DD) that forms an anti-parallel dimer. We derived a three-dimensional structural model of full-length talin at a resolution of approximately 2.5nm using EM reconstruction of full-length talin and the known shapes of the individual domains and inter-domain angles as derived from small angle X-ray scattering. Talin adopts a compact conformation consistent with a dimer in which the two talin rods form a donut-shaped structure, with the two talin heads packed side by side occupying the hole at the center of this donut. In this configuration, the integrin binding site in the head domain and the actin-binding site at the carboxy-terminus of the rod are masked, implying that talin must unravel before it can support integrin activation and engage the actin cytoskeleton.
authors.affiliation: Department of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK.
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Goult
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Xu
authors.forename: Alexandre R
authors.initials: AR
authors.lastname: Gingras
authors.forename: Mark
authors.initials: M
authors.lastname: Swift
authors.forename: Bipin
authors.initials: B
authors.lastname: Patel
authors.forename: Neil
authors.initials: N
authors.lastname: Bate
authors.forename: Petra M
authors.initials: PM
authors.lastname: Kopp
authors.forename: Igor L
authors.initials: IL
authors.lastname: Barsukov
authors.forename: David R
authors.initials: DR
authors.lastname: Critchley
authors.forename: Niels
authors.initials: N
authors.lastname: Volkmann
authors.forename: Dorit
authors.initials: D
authors.lastname: Hanein
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D003599:Cytoskeleton / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016608:Talin / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D000199:Actins; D010455:Peptides; D016608:Talin
keywords: Actin cytoskeleton; Electron microscopy; Focal adhesions; Integrin; NMR; SAXS