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RIAM and Vinculin Binding to Talin Are Mutually Exclusive and Regulate Adhesion Assembly and Turnover

DOI: 10.1074/jbc.M112.438119 DOI Help
PMID: 23389036 PMID Help

Authors: B. T. Goult (Department of Biochemistry, University of Leicester, U.K.) , Thomas Zacharchenko (School of Biological Sciences, University of Liverpool, U.K.) , N. Bate (Department of Biochemistry, University of Leicester, U.K.) , R. Tsang (Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, U.K.) , F. Hey (Department of Biochemistry, University of Leicester, U.K.) , Alex Gingras (Department of Biochemistry, University of Leicester) , Paul Elliott (School of Biological Sciences, University of Liverpool, U.K.) , G. C. K. Roberts (Department of Biochemistry, University of Leicester, U.K.) , C. Ballestrem (Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, U.K.) , D. R. Critchley (Department of Biochemistry, University of Leicester, U.K.) , I. L. Barsukov (School of Biological Sciences, University of Liverpool, U.K.)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Biological Chemistry , VOL 288 (12) , PAGES 8238 - 8249

State: Published (Approved)
Published: March 2013
Diamond Proposal Number(s): 8663 , 7044

Open Access Open Access

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.

Journal Keywords: Signal; Amino; Animals ; Binding; Binding ; Competitive ; Crystallography ; X-Ray ; Focal; Human; Humans ; Hydrophobic; Membrane; Mice ; Models ; Molecular ; Protein; Quaternary ; Protein; Secondary ; Talin ; Vinculin

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: I24-Microfocus Macromolecular Crystallography

Other Facilities: NO

Added On: 27/09/2014 21:04

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