Paine M J, Desmond H P, Theakston R D, Crampton J M
Snake Venom Research Unit, Liverpool School of Tropical Medicine, United Kingdom.
J Biol Chem. 1992 Nov 15;267(32):22869-76.
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.
一种名为矛头蝮蛇毒出血毒素（jararhagin）的大型出血毒素已从巴西矛头蝮蛇毒腺cDNA表达文库中克隆出来。该cDNA序列预测出一个由421个氨基酸残基组成的分子，其氨基酸序列与从竹叶青蛇（哈布蛇）毒液中分离出的一种高分子量出血性金属蛋白酶HR1B具有很强的同源性，且结构域结构相似。与HR1B一样，矛头蝮蛇毒出血毒素包含酶、解整合素和富含半胱氨酸的羧基末端区域。在解整合素区域，精氨酸-甘氨酸-天冬氨酸序列被谷氨酸-半胱氨酸-天冬氨酸取代，这在HR1B的非精氨酸-甘氨酸-天冬氨酸解整合素区域以及豚鼠精子融合蛋白PH-30β中也有发现。矛头蝮蛇毒出血毒素的cDNA序列预测出一种前体蛋白（原蛋白），它与解整合素肽trigramin和罗豆素原的前体中的隐蔽区域具有惊人的相似性。将矛头蝮蛇毒出血毒素与解整合素前体进行比较，突出了金属蛋白酶/解整合素家族中原蛋白、金属蛋白酶和解整合素结构域的模块化排列，并为它们的生物合成和进化提供了见解。
