Jararhagin and jaracetin: novel snake venom inhibitors of the integrin collagen receptor, alpha 2 beta 1.
Two novel proteins, jararhagin and jaracetin, were purified from Bothrops jararaca viper venom. Jararhagin is a 55-kDa member of the metalloprotease-disintegrin family. Jaracetin is a 60-kDa dimer representing a differently processed form of jararhagin. Like botrocetin, a previously described viper venom protein, jararhagin and jaracetin modulated binding of von Willebrand Factor to the glycoprotein Ib-IX complex on platelets through a specific interaction with the von Willebrand Factor A1 domain. Both jararhagin and jaracetin, but not botrocetin, also blocked alpha 2 beta 1-dependent platelet adhesion to collagen, a receptor interaction mediated through a homologous A domain on the integrin alpha 2 subunit.
De Luca
M
M
Hazel and Pip Appel Vascular Biology Laboratory, Baker Medical Research Institute, Prahran, Australia.
Ward
C M
CM
Ohmori
K
K
Andrews
R K
RK
Berndt
M C
MC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000187:drug effects; D001792:Blood Platelets / Q000378:metabolism*; D017837:Bothrops; D002852:Chromatography, Ion Exchange; D003094:Collagen; D003435:Crotalid Venoms / Q000302:isolation & purification / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D019012:Integrin beta1; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000187:drug effects; D007700:Kinetics; D008666:Metalloendopeptidases / Q000302:isolation & purification / Q000494:pharmacology*; D008970:Molecular Weight; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D038981:Receptors, Collagen; D018179:Receptors, Thrombin / Q000037:antagonists & inhibitors*; D014841:von Willebrand Factor / Q000378:metabolism; D000097146:Bothrops jararaca Venom
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D003094:Collagen; D003435:Crotalid Venoms; D019012:Integrin beta1; D016023:Integrins; D008666:Metalloendopeptidases; D010975:Platelet Aggregation Inhibitors; D038981:Receptors, Collagen; D018179:Receptors, Thrombin; D014841:von Willebrand Factor; D000097146:Bothrops jararaca Venom