Integrin receptors are involved in the attachment of adherent cells to the extracellular matrix and of lymphocytes to other cells. In these situations, talin codistributes with concentrations of integrins in the plasma membrane. Furthermore, in vitro binding studies suggest that integrins bind to talin, although with low affinity. Talin also binds with high affinity to vinculin, another cytoskeletal protein concentrated at points of cell adhesion. Finally, talin is a substrate for the calcium-ion activated protease, calpain II, which is also concentrated at points of cell–substratum contact.
Talin consists of a large C-terminal rod domain that contains bundles of alpha helices and an N-terminalFERM (band 4.1, ezrin, radixin, and moesin) domain with three subdomains: F1, F2, and F3. The F3 subdomain of the FERM domain contains the highest affinity integrin-binding site for integrin β tails and is sufficient to activate integrins.
Activation of the VBS leads to the recruitment of vinculin to form a complex with the integrins which aids stable cell adhesion. Formation of the complex between VBS and vinculin requires prior unfolding of this middle domain: once released from the talin hydrophobic core, the VBS helix is then available to induce the 'bundle conversion' conformational change within the vinculin head domain thereby displacing the intramolecular interaction with the vinculin tail, allowing vinculin to bind actin.
Vinculin binding sites are protein domains predominantly found in talin and talin-like molecules, enabling binding of vinculin to talin, stabilising integrin-mediated cell-matrix junctions. Talin, in turn, links integrins to the actin cytoskeleton.
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