Purification, cloning, and molecular characterization of a high molecular weight hemorrhagic metalloprotease, jararhagin, from Bothrops jararaca venom. Insights into the disintegrin gene family.
A large hemorrhagin, jararhagin, has been cloned from a Bothrops jararaca venom gland cDNA expression library. The cDNA sequence predicts a 421-amino acid residue molecule with strong amino acid sequence homology and similar domain structure to HR1B, a high molecular weight hemorrhagic metalloprotease isolated from Trimeresurus flavoviridis (Habu) venom. Like HR1B, jararhagin contains enzyme, disintegrin, and cysteine-rich carboxyl-terminal regions. In the disintegrin region, the Arg-Gly-Asp sequence is replaced by Glu-Cys-Asp, as found in non-Arg-Gly-Asp disintegrin regions of HR1B and a guinea pig sperm fusion protein PH-30 beta. The cDNA sequence of jararhagin predicts a precursor protein (proprotein) with striking similarity to cryptic regions in precursors of the disintegrin peptides trigramin and rhodostomin. Comparison of jararhagin with disintegrin precursors highlights the modular arrangement of proprotein, metalloprotease, and disintegrin domains in the metalloprotease/disintegrin family and provides an insight into their biosynthesis and evolution.
Paine
M J
MJ
Snake Venom Research Unit, Liverpool School of Tropical Medicine, United Kingdom.
Desmond
H P
HP
Theakston
R D
RD
Crampton
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D003435:Crotalid Venoms / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D019483:Disintegrins; D010450:Endopeptidases / Q000235:genetics* / Q000302:isolation & purification; D008666:Metalloendopeptidases / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D005810:Multigene Family; D010455:Peptides / Q000235:genetics*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000302:isolation & purification; D017386:Sequence Homology, Amino Acid; D012911:Snakes; D014688:Venoms / Q000235:genetics*; D000097146:Bothrops jararaca Venom
D003435:Crotalid Venoms; D004247:DNA; D019483:Disintegrins; D010450:Endopeptidases; D008666:Metalloendopeptidases; D010455:Peptides; D012313:RNA; D011994:Recombinant Proteins; D014688:Venoms; D000097146:Bothrops jararaca Venom; C041605:hemorrhagic proteinase IV