The structure of the C-terminal actin-binding domain of talin
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Alexandre R Gingras [1] ; Neil Bate [1] ; Benjamin T Goult [1] ; Larnele Hazelwood [4] ; Ilona Canestrelli [4] ; J Günter Grossmann [3] ; HongJun Liu [4] ; Nicholas S M Putz [1] ; Gordon C K Roberts [1] ; Niels Volkmann [4] ; Dorit Hanein [4] ; Igor L Barsukov [2] ; David R Critchley [1]
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[1] University of Leicester
University of Leicester
GB.ENG.H4.31UC, Reino Unido
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[2] University of Liverpool
University of Liverpool
Reino Unido
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[3] Daresbury Laboratory
Daresbury Laboratory
Reino Unido
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[4] Program of Infectious Diseases, Burnham Institute for Medical Research, La Jolla, CA, USA
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- Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 27, Nº. 2, 2007, págs. 458-469
- Idioma: inglés
- Enlaces
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Resumen
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.
