Characterization of the cross-linking site of disintegrins albolabrin, bitistatin, echistatin, and eristostatin on isolated human platelet integrin GPIIb/IIIa.
Disintegrins, a family of low molecular weight, RGD-containing peptides found in snake venoms prevent the binding of adhesive ligands to a number of integrin receptors. Albolabrin, bitistatin, echistatin, and eristostatin bind to the platelet fibrinogen receptor (GPIIb/IIIa) acting thus as potent inhibitors of platelet aggregation. Here, we have determined the cross-linking of these disintegrins on isolated GPIIb/IIIa. The cross-linking site of all of them was within GPIIIa 217-302, a domain that has been implicated in a number of receptor functions including heterodimer association, activation-dependent conformational changes, and fibrinogen binding.
Institut für Reproduktionsmedizin, Tierärztliche Hochschule, Hannover, FRG.
J J
JJ
Calvete
M A
MA
McLane
G J
GJ
Stewart
S
S
Niewiarowski
D000595:Amino Acid Sequence; D001665:Binding Sites; D003432:Cross-Linking Reagents; D003435:Crotalid Venoms / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism*; D012910:Snake Venoms; D014757:Viper Venoms / Q000378:metabolism* / Q000494:pharmacology
D003432:Cross-Linking Reagents; D003435:Crotalid Venoms; D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D012910:Snake Venoms; D014757:Viper Venoms; C057986:echistatin; C062186:bitistatin; C064595:albolabrin; C084060:eristostatin; C047981:arginyl-glycyl-aspartic acid