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Volume 271, Number 17, Issue of April 26, 1996 pp. 10365-10371
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
The Ligand Recognition Specificity of Integrins

(Received for publication, November 28, 1995; and in revised form, February 12, 1996)

Kazuhisa Suehiro Jeffrey W. Smith Edward F. Plow

alphabeta(3) (platelet membrane glycoprotein IIb-IIIa) and alpha(v)beta(3) are members of the beta(3) subfamily of integrin adhesion receptors. A cyclic peptide, KYGC(s-s)HarGDWPC(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 alphabeta(3) to examine the specificity of the beta(3) integrins. cHarGD interacted with high affinity with purified alphabeta(3) (K = 10 nM) or with platelets (K = 120 nM). While cHarGD was specific for alphabeta(3) in the presence of Ca, it bound to both beta(3) integrins in the presence of Mn. Barbourin, a snake venom disintegrin containing a reactive KGD sequence, remained alphabeta(3)-specific, even in the presence of Mn. cHarGD became cross-linked to a site in beta(3) of alphabeta(3), which is distinct from that of RGD peptides. These results allow identification of at least four classes of beta(3) ligands: Class I, represented by RGD peptides and vitronectin, react similarly with alphabeta(3) and alpha(v)beta(3); Class II, represented by cHarGD, -chain peptides and fibrinogen, react with both receptors in the presence of Mn but only with alphabeta(3) in the presence of Ca; Class III, represented by barbourin, are alphabeta(3)-specific under all cation conditions; Class IV, represented by osteopontin, bind primarily to alpha(v)beta(3).




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