The ligand recognition specificity of beta 3 integrins

alpha(IIb)beta(3) (platelet membrane glycoprotein IIb-IIa) and alpha(v) beta(3) are members of the beta(3) subfamily of integrin adhesion receptors. A cyclic peptide, KYGC(s-s)HarGDW-PC(s-s) (cHarGD), originally described by Scarborough et al. (Scarborough, R. M., Naughton, M. A., Teng, W., Rose, J. W., Phillips, D. R., Nannizzi, L., Arsten, A., Campbell, A. M., and Charo, I. F. (1993) J. Biol Chem. 268, 1066-1073) has been employed as a high affinity ligand for alpha(IIb)beta(3) to examine the specificity of the beta(3) integrins. cHarGD interacted with high affinity with purified alpha(IIb)beta(3) (K-d = 10 nm) or with platelets (K-d = 120 nM). While cHarGD was specific for alpha(IIb)beta(3)-specific, even in the presence of Mn2+. cHarGD became cross-linked to a site in beta(3) of alpha(IIb)beta(3), which is distinct from that of RGD peptides. These results allow identification of at lease four classes of beta(3) ligands: Class, I represented by RGD peptides and vitronectin, react similarly with alpha(IIb)beta(3) and alpha(v) beta(3); Class II, represented by cHarGD, gamma-chain peptides and fibrinogen, react with both receptors in the presence of Mn2+ but only with alpha(IIb)beta(3) in the presence of Ca2+; Class III, represented by barbourin, are alpha(IIb)beta(3)-specific under all cation conditions; Class IV, represented by osteopontin, bind primarily to alpha(v) beta(3).