Gingras, Alexandre R ORCID: 0000-0002-5373-0176, Bate, Neil, Goult, Benjamin T ORCID: 0000-0002-3438-2807, Hazelwood, Larnele, Canestrelli, Ilona, Grossmann, J Günter, Liu, HongJun, Putz, Nicholas SM, Roberts, Gordon CK ORCID: 0000-0001-6200-1373, Volkmann, Niels et al (show 3 more authors)
(2008)
The structure of the C-terminal actin-binding domain of talin.
The EMBO journal, 27 (2).
pp. 458-469.
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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.
Item Type: | Article |
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Additional Information: | SCB ## TULIP Type: Articles/Papers (Journal) ## |
Uncontrolled Keywords: | Animals, Rabbits, Mice, Actins, Peptide Fragments, Talin, Recombinant Proteins, Microscopy, Electron, Scanning, Crystallography, X-Ray, Magnetic Resonance Spectroscopy, Binding Sites, Amino Acid Sequence, Protein Structure, Secondary, Protein Structure, Tertiary, Protein Binding, Dimerization, Models, Biological, Image Processing, Computer-Assisted, Molecular Sequence Data |
Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
Depositing User: | Symplectic Admin |
Date Deposited: | 13 Mar 2024 09:32 |
Last Modified: | 15 Mar 2024 03:03 |
DOI: | 10.1038/sj.emboj.7601965 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3179354 |