RIAM and Vinculin Binding to Talin Are Mutually Exclusive and Regulate Adhesion Assembly and Turnover
Autor: | Neil Bate, Igor L. Barsukov, Thomas Zacharchenko, David R. Critchley, Gordon C. K. Roberts, Paul R. Elliott, Christoph Ballestrem, Ricky Tsang, Fiona Hey, Alexandre R. Gingras, Benjamin T. Goult |
---|---|
Rok vydání: | 2013 |
Předmět: |
Talin
Models Molecular Integrins Plasma protein binding Crystallography X-Ray environment and public health Biochemistry Protein Structure Secondary Mice Structural Biology RIAM Vinculin binding 0303 health sciences biology 030302 biochemistry & molecular biology food and beverages Vinculin 3. Good health Cell biology embryonic structures Protein Structure and Folding Adhesion Rap1 biological phenomena cell phenomena and immunity Hydrophobic and Hydrophilic Interactions Protein Binding animal structures Nuclear Magnetic Resonance Molecular Sequence Data Integrin macromolecular substances Binding Competitive Focal adhesion 03 medical and health sciences Human Umbilical Vein Endothelial Cells Animals Humans Protein Interaction Domains and Motifs Amino Acid Sequence Binding site Protein Structure Quaternary Cell adhesion Molecular Biology Adaptor Proteins Signal Transducing 030304 developmental biology Focal Adhesions Binding Sites Membrane Proteins Cell Biology biology.protein |
Zdroj: | The Journal of Biological Chemistry |
ISSN: | 0021-9258 |
DOI: | 10.1074/jbc.m112.438119 |
Popis: | Background: Talin mediates RIAM-dependent integrin activation and binds vinculin, which stabilizes adhesions. Results: Structural and biochemical data show that vinculin inhibits RIAM binding to the compact N-terminal region of the talin rod, a region essential for focal adhesion assembly. Conclusion: Talin·RIAM complexes activate integrins at the leading edge, whereas talin·vinculin promotes adhesion maturation. Significance: Talin changes partners in response to force-induced conformational change. 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. |
Databáze: | OpenAIRE |
Externí odkaz: |