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