Integrin connections to the cytoskeleton through talin and vinculin
- 20 March 2008
- journal article
- Published by Portland Press Ltd. in Biochemical Society Transactions
- Vol. 36 (2), 235-239
- https://doi.org/10.1042/bst0360235
Abstract
Integrins are αβ 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 β-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 β 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 α-actinin form interactions with vinculin.Keywords
This publication has 27 references indexed in Scilit:
- The structure and regulation of vinculinTrends in Cell Biology, 2006
- The Activity of the Vinculin Binding Sites in Talin Is Influenced by the Stability of the Helical Bundles That Make Up The Talin RodPublished by Elsevier BV ,2006
- Mapping and Consensus Sequence Identification for Multiple Vinculin Binding Sites within the Talin RodJournal of Biological Chemistry, 2005
- Cell Adhesion Strengthening: Contributions of Adhesive Area, Integrin Binding, and Focal Adhesion AssemblyMolecular Biology of the Cell, 2005
- A Vinculin Binding Domain from the Talin Rod Unfolds to Form a Complex with the Vinculin HeadStructure, 2005
- Activation of a vinculin-binding site in the talin rod involves rearrangement of a five-helix bundleThe EMBO Journal, 2004
- Structural basis for vinculin activation at sites of cell adhesionNature, 2004
- Integrins in MechanotransductionPublished by Elsevier BV ,2004
- Integrins: Bidirectional, Allosteric Signaling MachinesCell, 2002
- Dilated Cardiomyopathy Associated With Deficiency of the Cytoskeletal Protein MetavinculinCirculation, 1997