The overall shape of integrins is that of a globular 'head' supported by two rod like legs. The ligand-binding pocket is formed by the combination of A-domain or beta-I domain on the beta3 subunit and the putative beta-propeller fold on the alphaIIb subunit in the head regions. The binding of ligand to integrin is also dependent on divalent cations (usually Mn++ or Mg++or Ca++). A conserved motif, the metal ion-dependant adhesion site (MIDAS) is located in the alpha and the beta chains that coordinate the divalent cation at the top of the domain.
Active integrin alphaIIb beta3 interacts with a variety of plasma proteins such as fibrinogen, vWF, thrombin, thrombospondin, and fibronectin. The ability of alphaIIbbeta3 to bind fibrinogen plays a crucial role in platelet aggregation and hemostasis. Most of these matrix proteins have integrin binding sites of 3-6 amino acids length, of which the best known are the 'RGD' and 'KGD' motifs. The alpha and beta integrin subunits are both required for ligand binding.