Article

  • The EMBO Journal (2008) 27, 458 - 469
  • doi:10.1038/sj.emboj.7601965

Published online: 20 December 2007

The structure of the C-terminal actin-binding domain of talinEMBO Open

Alexandre R Gingras1, Neil Bate1, Benjamin T Goult1, Larnele Hazelwood2, Ilona Canestrelli2, J Günter Grossmann3, HongJun Liu2, Nicholas S M Putz1, Gordon C K Roberts1, Niels Volkmann2, Dorit Hanein2, Igor L Barsukov4 and David R Critchley1

  1. Department of Biochemistry, University of Leicester, Leicester, UK
  2. Program of Infectious Diseases, Burnham Institute for Medical Research, La Jolla, CA, USA
  3. Molecular Biophysics Group, Science and Technology Facilities Council Daresbury Laboratory, Warrington, UK
  4. School of Biological Sciences, University of Liverpool, Liverpool, UK

Correspondence to:

David R Critchley, Department of Biochemistry, University of Leicester, Lancaster Road, Henry Wellcome Building, Leicester LE1 9HN, UK. Tel.: +44 116 229 7099; Fax: +44 116 252 5097; E-mail: drc@le.ac.uk

Received 2 August 2007; Accepted 29 November 2007


Talin is a large dimeric protein that couples integrins to cytoskeletal actin. Here, we report the structure of the C-terminal actin-binding domain of talin, the core of which is a five-helix bundle linked to a C-terminal helix responsible for dimerisation. The NMR structure of the bundle reveals a conserved surface-exposed hydrophobic patch surrounded by positively charged groups. We have mapped the actin-binding site to this surface and shown that helix 1 on the opposite side of the bundle negatively regulates actin binding. The crystal structure of the dimerisation helix reveals an antiparallel coiled-coil with conserved residues clustered on the solvent-exposed face. Mutagenesis shows that dimerisation is essential for filamentous actin (F-actin) binding and indicates that the dimerisation helix itself contributes to binding. We have used these structures together with small angle X-ray scattering to derive a model of the entire domain. Electron microscopy provides direct evidence for binding of the dimer to F-actin and indicates that it binds to three monomers along the long-pitch helix of the actin filament.

  • Keywords:

    • actin,
    • electron microscopy,
    • structure,
    • talin,
    • THATCH domain

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation or the creation of derivative works without specific permission.

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