The structural bases of integrin-ligand interactions.

Many extracellular matrix (ECM) proteins, particularly those in the vascular system, use their classical integrin-recognition motif Arg-Gly-Asp (RGD) to interact with integrins. The RGD motif is generally located in flexible peptide loops whose variable conformation enables the relatively few integrins with broad specificity, such as alpha(v)beta(3) and alpha(IIb)beta(3), to bind to a large variety of different ECM proteins. However, certain ECM constituents, such as collagens and laminins, interact with integrins in a conformation-dependent manner, in which both the linear structure and spatial arrangement of the polypeptides are important for the formation of active binding sites. These interactions provide high specificity for the communication of cells with distinct members of the ECM.