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A vinculin-binding domain from the talin rod unfolds to form a complex with the vinculin head

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journal contribution
posted on 10.12.2007, 10:26 by Ian Fillingham, Alexandre R. Gingras, Evangelos Papagrigoriou, Bipin Patel, Jonas Emsley, David R. Critchley, Gordon C.K. Roberts, Igor L. Barsukov
The cytoskeletal protein talin plays a key role in activating integrins and in coupling them to the actin cytoskeleton. Its N-terminal globular head, which binds β-integrins, is linked to an extended rod having a C-terminal actin-binding site and several vinculin-binding sites (VBSs). The NMR structure of residues 755-889 of the rod (containing a VBS) is shown to be an amphipathic 4-helix bundle with a left-handed topology. A talin peptide corresponding to the VBS binds the vinculin head; the X-ray crystallographic structure of this complex shows that the residues which interact with vinculin are buried in the hydrophobic core of the talin fragment. NMR shows that the interaction involves a major structural change in the talin fragment, including unfolding of one of its helices, making the VBS accessible to vinculin. Interestingly, the talin 755-889 fragment binds more than one vinculin head molecule, suggesting that the talin rod may contain additional as yet unrecognised VBSs.

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Citation

Structure, 2005, 13 (1), pp. 65-74

Version

AM (Accepted Manuscript)

Published in

Structure

Publisher

Elsevier (Cell Press)

issn

0969-2126

Copyright date

2005

Available date

10/12/2007

Publisher version

http://www.sciencedirect.com/science/article/pii/S096921260400382X

Language

en

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