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- PMID: 23389036
- UKPMCID: 23389036
- DOI: 10.1074/jbc.M112.438119
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RIAM and vinculin binding to talin are mutually exclusive and regulate adhesion assembly and turnover.
Goult, Benjamin T; Zacharchenko, Tom; Bate, Neil; Tsang, Ricky; Hey, Fiona; Gingras, Alexandre R; Elliott, Paul R; Roberts, Gordon C K; Ballestrem, Christoph; Critchley, David R; Barsukov, Igor L
The Journal of biological chemistry. 2013;.
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Full-text held externally
- PMID: 23389036
- UKPMCID: 23389036
- DOI: 10.1074/jbc.M112.438119
Abstract
Talin activates integrins, couples them to F-actin and recruits vinculin to focal adhesions (FAs). Here we report the structural characterization of the talin rod, 13 helical bundles (R1-R13) organized into a compact cluster of 4-helix bundles (R2-R4) within a linear chain of 5-helix bundles. Nine of the bundles contain vinculin-binding sites (VBSs) - R2R3 are atypical each containing two VBSs. Talin R2R3 also binds synergistically to RIAM, a Rap1 effector involved in integrin activation. Biochemical and structural data show that vinculin and RIAM binding to R2R3 is mutually exclusive. Moreover, vinculin binding requires domain unfolding while RIAM binds the folded R2R3 double domain. In cells, RIAM is enriched in nascent adhesions at the leading edge whereas vinculin is enriched in FAs, and expression of the talin-binding domain of vinculin displaces RIAM from FAs. We propose a model in which RIAM binding to R2R3 initially recruits talin to membranes where it activates integrins. As talin engages F-actin, force exerted on R2R3 disrupts RIAM binding and exposes the VBSs, which recruit vinculin to stabilize the complex.