Control of high affinity interactions in the talin C terminus: how talin domains coordinate protein dynamics in cell adhesions.
In cell-extracellular matrix junctions (focal adhesions), the cytoskeletal protein talin is central to the connection of integrins to the actin cytoskeleton. Talin is thought to mediate this connection via its two integrin, (at least) three actin, and several vinculin binding sites. The binding sites are cryptic in the head-to-rod autoinhibited cytoplasmic form of the protein and require (stepwise) conformational activation. This activation process, however, remains poorly understood, and there are contradictory models with respect to the determinants of adhesion site localization. Here, we report turnover rates and protein-protein interactions in a range of talin rod domain constructs varying in helix bundle structure. We conclude that several bundles of the C terminus cooperate to regulate targeting and concomitantly tailor high affinity interactions of the talin rod in cell adhesions. Intrinsic control of ligand binding activities is essential for the coordination of adhesion site function of talin.
Himmel
Mirko
M
Interdisciplinary Centre for Clinical Research (IZKF) Leipzig, Faculty of Medicine, University of Leipzig, D-04103 Leipzig, Germany.
Ritter
Anett
A
Interdisciplinary Centre for Clinical Research (IZKF) Leipzig, Faculty of Medicine, University of Leipzig, D-04103 Leipzig, Germany.
Rothemund
Sven
S
Interdisciplinary Centre for Clinical Research (IZKF) Leipzig, Faculty of Medicine, University of Leipzig, D-04103 Leipzig, Germany.
Pauling
Björg V
BV
Zoological Institute, Technical University of Braunschweig, D-38106 Braunschweig, Germany.
Rottner
Klemens
K
Cytoskeleton Dynamics Group, Helmholtz Centre for Infection Research, D-38124 Braunschweig, Germany.
Gingras
Alexandre R
AR
Department of Biochemistry, University of Leicester, Leicester LE1 9HN, United Kingdom.
Ziegler
Wolfgang H
WH
Interdisciplinary Centre for Clinical Research (IZKF) Leipzig, Faculty of Medicine, University of Leipzig, D-04103 Leipzig, Germany. Electronic address: wolfgang.ziegler@medizin.uni-leipzig.de.
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism*; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D017433:Protein Structure, Secondary / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D016608:Talin / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D016023:Integrins; D016608:Talin; C496077:Tln1 protein, mouse