The von willebrand factor domain-mediating botrocetin-induced binding to glycoprotein IB lies between Val449 and Lys728.
Botrocetin, a component of Bothrops jararaca venom, induces von Willebrand factor (vWF)-dependent platelet agglutination and has been proposed as an alternative agent to ristocetin for evaluating vWF function. However, important differences between the vWF-platelet interactions induced by these two agents have suggested that different regions of vWF and the platelet may be involved in the interactions induced by the two agonists. We have recently demonstrated that binding of vWF to the platelet glycoprotein (GP) Ib receptor, either induced by ristocetin or as occurs spontaneously with asialo-vWF or vWF from IIb von Willebrand disease, is mediated by a domain residing on a 52/48-kilodalton (kD) tryptic fragment of vWF. This fragment extends from amino acid residue Val (449) to Lys (728). We have now found that this 52/48-kD fragment blocks botrocetin-induced binding of vWF to platelets and completely inhibits botrocetin-induced platelet agglutination. These results provide evidence that the vWF domain-mediating, botrocetin-induced platelet agglutination lies within the region delimited by this fragment and is therefore close to or identical with that which mediates ristocetin-induced binding and spontaneous binding of vWF to platelet GPIb. Anti-GPIb monoclonal antibodies also blocked agglutination, which showed that botrocetin, like ristocetin, induces binding of vWF to the GPIb receptor.
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D001792:Blood Platelets / Q000378:metabolism; D003435:Crotalid Venoms / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D014841:von Willebrand Factor / Q000235:genetics* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D003435:Crotalid Venoms; D010980:Platelet Membrane Glycoproteins; D014841:von Willebrand Factor; C030961:botrocetin