Integrin connections to the cytoskeleton through talin and vinculin.
Integrins are alphabeta heterodimeric receptors that mediate attachment of cells to the extracellular matrix and therefore play important roles in cell adhesion, migration, proliferation and survival. Among the cytoskeletal proteins that interact directly with the beta-chain cytoplasmic domain, talin has emerged as playing a critical role in integrin activation and linkage to the actin cytoskeleton. Talin (2541 amino acids) is an elongated (60 nm) flexible antiparallel dimer, with a small globular head connected to an extended rod. The talin head contains a FERM (4.1/ezrin/radixin/moesin) domain (residues 86-400) with binding sites for several beta integrin cytodomains and the talin rod contains a second lower-affinity integrin-binding site, a highly conserved C-terminal actin-binding site and also several binding sites for vinculin. We have determined previously the crystal structures of two domains from the talin rod, spanning residues 482-789. Talin-(482-655), which contains a VBS (vinculin-binding site), folds into a five-helix bundle whereas talin-(656-789) is a four-helix bundle. We have also reported the crystal structure of the N-terminal vinculin head domain in complex with an activated form of talin. In the present paper, we consider how binding sites buried within the folded helical bundles of talin and alpha-actinin form interactions with vinculin.
Ziegler
Wolfgang H
WH
IZKF Leipzig, Faculty of Medicine, University of Leipzig, Inselstrasse 22, D-04103 Leipzig, Germany.
Gingras
Alex R
AR
Critchley
David R
DR
Emsley
Jonas
J
D000185:Actinin / Q000737:chemistry / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D003599:Cytoskeleton / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000502:physiology*; D008958:Models, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016608:Talin / Q000737:chemistry / Q000502:physiology*; D016596:Vinculin / Q000737:chemistry / Q000502:physiology*
D016023:Integrins; D016608:Talin; D000185:Actinin; D016596:Vinculin