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EMBO J. 2004 Aug 4;23(15):2942-51. Epub 2004 Jul 22.

Activation of a vinculin-binding site in the talin rod involves rearrangement of a five-helix bundle.

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  • 1Department of Biochemistry, University of Leicester, Leicester, UK.

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.

PMID:
15272303
[PubMed - indexed for MEDLINE]
PMCID:
PMC514914
Free PMC Article

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