Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/14362
Title: Activation of a vinculin-binding site in the talin rod involves rearrangement of a five-helix bundle.
Authors: Papagrigoriou, E
Gingras, AR
Barsukov, IL
Bate, N
Fillingham, IJ
Patel, B
Frank, R
Ziegler, WH
Roberts, GC
Critchley, DR
Emsley, J
First Published: 4-Aug-2004
Citation: EMBO J, 2004, 23 (15), pp. 2942-2951
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.
DOI Link: 10.1038/sj.emboj.7600285
ISSN: 0261-4189
Links: http://hdl.handle.net/2381/14362
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Biochemistry

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