Activation of a vinculin‐binding site in the talin rod involves rearrangement of a five‐helix bundle
By E. Papagrigoriou, A. Gingras, I. Barsukov, N. Bate, I. Fillingham, B. Patel, R. Frank, W. Ziegler, G. Roberts, D. Critchley and 1 more. 2004
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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.
Subfields: Cell Biology
View Paper: https://www.semanticscholar.org/paper/8464a00e8064b4813f6e9c8dc6530947e09ec72c
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In Cell Biology
Citations in the corpus
- Genetic and cell biological analysis of integrin outside-in signaling. (2009, background): “Vinculin binds to several sites in the talin rod (Critchley and Gingras 2008) that are normally buried in helical bundles but may become exposed upon mechanical stretch (Papagrigoriou et al. 2004; Fillingham et al. 2005; Lee et al. 2007).”