Goult, Benjamin T 
ORCID: 0000-0002-3438-2807, Zacharchenko, Thomas, Bate, Neil, Tsang, Ricky, Hey, Fiona, Gingras, Alexandre R ORCID: 0000-0002-5373-0176, Elliott, Paul R ORCID: 0000-0002-7641-2103, Roberts, Gordon CK ORCID: 0000-0001-6200-1373, Ballestrem, Christoph ORCID: 0000-0002-5375-7985, Critchley, David R et al (show 1 more authors)
(2013)
RIAM and vinculin binding to talin are mutually exclusive and regulate adhesion assembly and turnover.
The Journal of biological chemistry, 288 (12).
pp. 8238-8249.
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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 four-helix bundles (R2-R4) within a linear chain of five-helix bundles. Nine of the bundles contain vinculin-binding sites (VBS); R2R3 are atypical, with each containing two VBS. 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, whereas 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. 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 VBS, which recruit vinculin to stabilize the complex.
| Item Type: | Article |
|---|---|
| Additional Information: | ## TULIP Type: Articles/Papers (Journal) ## |
| Uncontrolled Keywords: | Focal Adhesions, Animals, Humans, Mice, Adaptor Proteins, Signal Transducing, Talin, Vinculin, Membrane Proteins, Crystallography, X-Ray, Binding Sites, Binding, Competitive, Amino Acid Sequence, Protein Structure, Quaternary, Protein Structure, Secondary, Protein Binding, Models, Molecular, Molecular Sequence Data, Protein Interaction Domains and Motifs, Hydrophobic and Hydrophilic Interactions, Human Umbilical Vein Endothelial Cells |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 13 Mar 2024 09:34 |
| Last Modified: | 13 Mar 2024 09:34 |
| DOI: | 10.1074/jbc.m112.438119 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3179350 |
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