A novel disintegrin-like domain of a high molecular weight metalloprotease inhibits platelet aggregation.
Disintegrin is one of the functionally distinct domains in high molecular weight metalloproteases from various snake venoms and generally has an Arg-Gly-Asp (RGD) sequence that is recognized by specific cell surface integrins. A cDNA encoding the disintegrin-like domain of a snake venom metalloprotease was cloned, expressed in Pichia pastoris, and molecular function of the recombinant protein was characterized. The cDNA sequence indicated that the disintegrin-like domain contains an Asp-Glu-Cys-Asp (DECD) sequence in place of the RGD motif. The expressed disintegrin-like protein was designated as halydin and it was able to inhibit human platelet aggregation in a dose-dependent manner. Unlike other typical RGD-disintegrins, the recombinant non-RGD disintegrin, halydin, inhibited platelet aggregation by suppressing platelet adhesion to collagen rather than by blocking fibrinogen binding to glycoprotein (GP) IIb-IIIa on the platelet surface. Experimental evidence suggests that halydin binds to integrin alpha2beta1 on the platelet surface.
You
Weon-Kyoo
WK
Department of Biochemistry, College of Science, Yonsei University, Seoul 120-749, South Korea.
Jang
Yoon-Jung
YJ
Chung
Kwang-Hoe
KH
Kim
Doo-Sik
DS
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D003435:Crotalid Venoms / Q000201:enzymology; D019483:Disintegrins / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016023:Integrins / Q000502:physiology; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010973:Platelet Adhesiveness / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D017434:Protein Structure, Tertiary
D003435:Crotalid Venoms; D019483:Disintegrins; D016023:Integrins; D010975:Platelet Aggregation Inhibitors; D008666:Metalloendopeptidases; C478162:halydin protein, Gloydius halys