The complete amino acid sequence of the high molecular mass hemorrhagic protein HR1B isolated from the venom of Trimeresurus flavoviridis.
Hemorrhage is a common occurrence in a victim bitten by crotalid and viperid snakes, and hemorrhagic components in these various venoms have been isolated and characterized. Previously, we have shown that a low molecular weight hemorrhagic protein (HR2a, 202 amino acid residues) isolated from the venom of Trimeresurus flavoviridis is a member of a new subfamily of metalloproteinases. We now report the complete amino acid sequence of a high molecular mass hemorrhagic protein isolated from the same venom. This protein, HR1B, is a mosaic protein composed of 416 residues containing four asparagine-linked oligosaccharide chains. The amino-terminal half (residues 1-203) of HR1B contains a metalloproteinase domain, the sequence of which is 62% identical to that of HR2a and 52% identical to that of hemorrhagic toxin d isolated from Crotalus atrox venom. The most interesting finding is that the middle region (residues 204-300) of HR1B shows a striking similarity to disintegrins, Arg-Gly-Asp-containing platelet aggregation inhibitors, recently found in several viper venoms. Interestingly, however, this region of HR1B does not contain the Arg-Gly-Asp sequence which is known to be a putative binding site in the disintegrins for the platelet fibrinogen receptor, the glycoprotein IIb-IIIa complex. We also found that the carboxyl-terminal region (residues 213-336) of the middle part of HR1B shows 30% identity to residues 1543-1656 of von Willebrand factor and that the remaining region at the carboxyl-terminal end is unique and has a cysteine-rich sequence. These results suggest that the middle portion of HR1B, which shows structural similarities to the disintegrins and von Willebrand factor, may be important in synergistically stimulating hemorrhagic activity in the NH2-terminal metalloproteinase domain.
Department of Molecular Biology, Graduate School of Medical Science, Faculty of Science, Kyushu University, Fukuoka, Japan.
H
H
Takeya
K
K
Oda
T
T
Miyata
T
T
Omori-Satoh
S
S
Iwanaga
D000595:Amino Acid Sequence; D000818:Animals; D003435:Crotalid Venoms / Q000235:genetics* / Q000302:isolation & purification; D003488:Cyanogen Bromide; D006801:Humans; D008666:Metalloendopeptidases / Q000235:genetics*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000302:isolation & purification; D012689:Sequence Homology, Nucleic Acid; D012911:Snakes; D014841:von Willebrand Factor / Q000235:genetics
D003435:Crotalid Venoms; D010446:Peptide Fragments; C065690:hemorrhagic toxin HR-1b; D014841:von Willebrand Factor; D008666:Metalloendopeptidases; D003488:Cyanogen Bromide