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LD Motif Recognition by Talin: Structure of the Talin-DLC1 Complex

DOI: 10.1016/j.str.2016.04.016 DOI Help

Authors: Thomas Zacharchenko (Institute of Integrative Biology, University of Liverpool, Diamond Light Source) , Xiaolan Qian (Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health) , Benjamin T. Goult (School of Biosciences, University of Kent) , Devina Jethwa (Wellcome Trust Centre for Cell-Matrix Research, University of Manchester) , Teresa B. Almeida (Institute of Integrative Biology, University of Liverpool) , Christoph Ballestrem (Wellcome Trust Centre for Cell-Matrix Research, University of Manchester) , David R. Critchley (Department of Biochemistry, University of Leicester) , Douglas R. Lowy (Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health) , Igor L. Barsukov (Institute of Integrative Biology, University of Liverpool)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Structure , VOL 24 , PAGES 1130 - 1141

State: Published (Approved)
Published: July 2016

Open Access Open Access

Abstract: Cell migration requires coordination between integrin-mediated cell adhesion to the extracellular matrix and force applied to adhesion sites. Talin plays a key role in coupling integrin receptors to the actomyosin contractile machinery, while deleted in liver cancer 1 (DLC1) is a Rho GAP that binds talin and regulates Rho, and therefore actomyosin contractility. We show that the LD motif of DLC1 forms a helix that binds to the four-helix bundle of the talin R8 domain in a canonical triple-helix arrangement. We demonstrate that the same R8 surface interacts with the paxillin LD1 and LD2 motifs. We identify key charged residues that stabilize the R8 interactions with LD motifs and demonstrate their importance in vitro and in cells. Our results suggest a network of competitive interactions in adhesion complexes that involve LD motifs, and identify mutations that can be used to analyze the biological roles of specific protein-protein interactions in cell migration.

Subject Areas: Biology and Bio-materials, Chemistry, Medicine


Instruments: I03-Macromolecular Crystallography

Added On: 12/09/2016 15:49

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