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Activation of a vinculin‐binding site in the talin rod involves rearrangement of a five‐helix bundle
Author(s) -
Papagrigoriou Evangelos,
Gingras Alexandre R,
Barsukov Igor L,
Bate Neil,
Fillingham Ian J,
Patel Bipin,
Frank Ronald,
Ziegler Wolfgang H,
Roberts Gordon CK,
Critchley David R,
Emsley Jonas
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600285
Subject(s) - vinculin , helix (gastropod) , integrin , helix bundle , focal adhesion , biophysics , cytoskeleton , biology , alpha helix , protein structure , microbiology and biotechnology , crystallography , biochemistry , chemistry , cell , signal transduction , ecology , snail
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.