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- Title
Activation of a vinculin-binding site in the talin rod involves rearrangement of a five-helix bundle.
- Authors
Papagrigoriou, Evangelos; Gingras, Alexandre R; Barsukov, Igor L; Bate, Neil; Fillingham, Ian J; Patel, Bipin; Frank, Ronald; Ziegler, Wolfgang H; Roberts, Gordon C K; Critchley, David R; Emsley, Jonas
- 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.
- Publication
The EMBO journal, 2004, Vol 23, Issue 15, p2942
- ISSN
0261-4189
- Publication type
Journal Article
- DOI
10.1038/sj.emboj.7600285