FIGURE 7.

Model for αIIbβ3 activity regulation by talin. A, upper diagram, integrins (αIIb, green; β3 blue) are present on the surface of CHO cells or platelets in a non-clustered, bent, low affinity state. Talin (fuchsia) in the cytoplasm is inhibited from binding to integrins due to intra- or intermolecular interactions between its head and tail domains. Unbound multivalent ligands are shown as black lines with triangles for binding motifs. Middle diagrams, upon activation of platelets, the inhibition of talin is released, and it binds to the cytoplasmic domains of the β3 subunit resulting in clustered integrins. This clustering may leave the integrins in the bent state or a new conformation, but in either case, the integrin remains in a low affinity state (represented by vertical blue rectangles). The increase in clustering results in multiple low affinity interactions between ligand and integrins. Lower diagram, binding of ligand to the integrins triggers a change in integrin head domains so that they are ultimately in a high affinity state (represented by diagonal blue rectangles). B, in the absence of clustering, integrins interact with ligands and promote a change in affinity of individual integrins. Upon dissociation, they return to their low affinity state.