Article
- The EMBO Journal (2004) 23, 2942 - 2951
- doi:10.1038/sj.emboj.7600285
Published online: 22 July 2004
Subject Categories:
Activation of a vinculin-binding site in the talin rod involves rearrangement of a five-helix bundle
Evangelos Papagrigoriou1, Alexandre R Gingras1, Igor L Barsukov1, Neil Bate1, Ian J Fillingham1, Bipin Patel1, Ronald Frank2, Wolfgang H Ziegler3, Gordon CK Roberts1, David R Critchley1 and Jonas Emsley1,4
- Department of Biochemistry, University of Leicester, Leicester, UK
- Department of Chemical Biology, German Research Centre for Biotechnology (GBF), Braunschweig, Germany
- Zoological Institute, Technical University of Braunschweig, Braunschweig, Germany
- Present address: Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK
Correspondence to:
Jonas Emsley, Department of Biochemistry, University of Leicester, Leicester LE1 7RH, UK. Tel: +44 116 252 5143; Fax: +44 116 252 3473; E-mail: jonas.emsley@nottingham.ac.uk or je14@leicester.ac.uk
Received 20 April 2004; Accepted 3 June 2004
Abstract
The interaction between the cytoskeletal proteins talin and vinculin plays a key role in integrin-mediated cell adhesion and migration. We have determined the crystal structures of two domains from the talin rod spanning residues 482–789. Talin 482–655, which contains a vinculin-binding site (VBS), folds into a five-helix bundle whereas talin 656–789 is a four-helix bundle. We show that the VBS is composed of a hydrophobic surface spanning five turns of helix 4. All the key side chains from the VBS are buried and contribute to the hydrophobic core of the talin 482–655 fold. We demonstrate that the talin 482–655 five-helix bundle represents an inactive conformation, and mutations that disrupt the hydrophobic core or deletion of helix 5 are required to induce an active conformation in which the VBS is exposed. We also report the crystal structure of the N-terminal vinculin head domain in complex with an activated form of talin. Activation of the VBS in talin and the recruitment of vinculin may support the maturation of small integrin/talin complexes into more stable adhesions.
Keywords:
- focal adhesions,
- integrin,
- talin,
- vinculin
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