|
 |
|
|
| Subject Categories: Cell & Tissue Architecture | Structural Biology |
|
| 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 talin EMBO 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 To whom correspondence should be addressed 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; Published online 20 December 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 |
|
|
|
Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSCell biology How to build a cell junction Nature News and Views (29 Jul 2004) Plugging into actin's architectonic socket Nature Structural Biology News and Views (01 Mar 1997) RESEARCHThe structure of the C-terminal actin-binding domain of talin The EMBO Journal Article Structural definition of the F-actin?binding THATCH domain from HIP1R Nature Structural & Molecular Biology Article (01 Feb 2006) |
|
|
| |
| |
| |
 | Email link to a friend |
| |
 | Download PDF |
| |
 | Full text |
| |
| |
| |
 | Previous article |
| |
 | Table of contents |
| |
| |
 | Rights and permissions |
| |
 | Reprints |
| |
| |
| |
 Register for table of contents by email | |
| |
| |
| |