Article
- The EMBO Journal (2008) 27, 458 - 469
- doi:10.1038/sj.emboj.7601965
Published online: 20 December 2007
Subject Categories:
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
- Department of Biochemistry, University of Leicester, Leicester, UK
- Program of Infectious Diseases, Burnham Institute for Medical Research, La Jolla, CA, USA
- Molecular Biophysics Group, Science and Technology Facilities Council Daresbury Laboratory, Warrington, UK
- 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
Abstract
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
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