The ligand recognition specificity of beta3 integrins.
AlphaIIbbeta3 (platelet membrane glycoprotein IIb-IIIa) and alphavbeta3 are members of the beta3 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 alphaIIbbeta3 to examine the specificity of the beta3 integrins. cHarGD interacted with high affinity with purified alphaIIbbeta3 (Kd = 10 nM) or with platelets (Kd = 120 nM). While cHarGD was specific for alphaIIbbeta3 in the presence of Ca2+, it bound to both beta3 integrins in the presence of Mn2+. Barbourin, a snake venom disintegrin containing a reactive KGD sequence, remained alphaIIbbeta3-specific, even in the presence of Mn2+. cHarGD became cross-linked to a site in beta3 of alphaIIb beta3, which is distinct from that of RGD peptides. These results allow identification of at least four classes of beta3 ligands: Class I, represented by RGD peptides and vitronectin, react similarly with alphaIIbbeta3 and alphavbeta3; Class II, represented by cHarGD, gamma-chain peptides and fibrinogen, react with both receptors in the presence of Mn2+ but only with alphaIIbbeta3 in the presence of Ca2+; Class III, represented by barbourin, are alphaIIbbeta3-specific under all cation conditions; Class IV, represented by osteopontin, bind primarily to alphavbeta3.
Suehiro
K
K
Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Smith
J W
JW
Plow
E F
EF
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry*; D001792:Blood Platelets / Q000378:metabolism; D002413:Cations, Divalent; D002478:Cells, Cultured; D003435:Crotalid Venoms / Q000737:chemistry; D005340:Fibrinogen / Q000378:metabolism; D006709:Homoarginine / Q000737:chemistry; D006801:Humans; D039661:Integrin beta3; D016023:Integrins / Q000737:chemistry*; D008024:Ligands; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry; D010456:Peptides, Cyclic / Q000737:chemistry; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry*; D016024:Receptors, Cytoadhesin / Q000737:chemistry*
D015703:Antigens, CD; D002413:Cations, Divalent; D003435:Crotalid Venoms; D039661:Integrin beta3; D016023:Integrins; D008024:Ligands; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010980:Platelet Membrane Glycoproteins; D016024:Receptors, Cytoadhesin; C098931:lysyl-tyrosyl-glycyl-cysteinyl-homoarginyl-glycyl-aspartyl-tryptophyl-prolyl-cysteine cyclic (4-10)-disulfide; C068858:barbourin; D006709:Homoarginine; C047981:arginyl-glycyl-aspartic acid; D005340:Fibrinogen