A C-type lectin-like protein from Agkistrodon acutus venom binds to both platelet glycoprotein Ib and coagulation factor IX/factor X.
Agkisacutacin, a C-type lectin-like protein (CLP) isolated from Agkistrodon acutus venom, had been previously identified as an antagonist of platelet aggregation induced by ristocetin, as well as a certain extent fibrinogenlytic activity. In this study, agkisacutacin was further purified by three-step chromatography, and its biological functions were characterized. Agkisacutacin after further purification retained the effect on ristocetin-induced, von Willebrand factor-dependent platelet aggregation, while it lost the fibrinogenlytic activity. FACS and ELISA assays showed that agkisacutacin belongs to membrane glycoprotein Ib-binding protein (GPIb-bp) for it could block and inhibit the binding of anti-GPIb antibody to GPIb. Especially, agkisacutacin exhibits anti-coagulant activity and the function as IX/X-binding protein was confirmed by PAGE and ELISA. So, agkisacutacin is the first reported CLP that binds to both platelet membrane receptors and coagulation factors.
Li
Wei-Fang
WF
School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, PR China.
Chen
Lan
L
Li
Xiang-Ming
XM
Liu
Jing
J
D017836:Agkistrodon / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D000925:Anticoagulants / Q000302:isolation & purification / Q000378:metabolism; D003435:Crotalid Venoms / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D005164:Factor IX / Q000378:metabolism*; D005170:Factor X / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D037181:Lectins, C-Type / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010974:Platelet Aggregation / Q000187:drug effects; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D011485:Protein Binding; D012310:Ristocetin / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid
C031442:Agkistrodon venoms; D000925:Anticoagulants; D003435:Crotalid Venoms; D037181:Lectins, C-Type; D019038:Platelet Glycoprotein GPIb-IX Complex; C401844:agkisacutacin; D012310:Ristocetin; D005164:Factor IX; D005170:Factor X; C041603:Agkistrodon platelet aggregation inhibitor