Evidence for heterogeneous forms of the snake venom metalloproteinase jararhagin: a factor contributing to snake venom variability
Evidence for heterogeneous forms of the snake venom metalloproteinase jararhagin: a factor contributing to snake venom variability
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DOI：
10.1016/s0003-9861(02)00598-2
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发表时间：
2003-01-15
影响因子：
3.9
通讯作者：
Fox, JW
中科院分区：
文献类型：
--
作者：
Moura-da-Silva, AM;Della-Casa, MS;Fox, JW
金属蛋白酶的蛇毒金属蛋白酶亚家族包括蛇毒金属蛋白酶（SVMP）和哺乳动物解聚素/金属蛋白酶。这些蛋白质作为酶原合成，并经历蛋白水解加工，产生多种多功能蛋白质。贾拉哈金是从巴西矛头蝮蛇毒液中分离出的一种P - III型蛇毒金属蛋白酶。在粗毒液中，通常发现两种形式的贾拉哈金，即全长贾拉哈金和贾拉哈金 - C，贾拉哈金 - C是贾拉哈金经蛋白水解加工后的形式，由贾拉哈金的解聚素样结构域和富含半胱氨酸的结构域组成。为了更好地理解巴西矛头蝮蛇毒液中这些贾拉哈金形式的结构和作用机制基础以及一般毒液复杂性的来源，我们研究了从毒液中分离出的贾拉哈金形式以及在不同pH值、钙离子浓度和还原剂条件下分离出的贾拉哈金的自溶情况。从我们的研究结果来看，从毒液中分离出的贾拉哈金呈现两种形式：一种主要形式在体外自溶过程中稳定，一种次要形式在多种条件下（包括碱性pH值、低钙离子浓度或还原剂存在）易发生自溶。从分离出的贾拉哈金产生贾拉哈金 - C的自溶位点与从粗毒液中分离出的贾拉哈金 - C所观察到的位点不同。综上所述，这些数据使我们得出结论：在毒液腺中贾拉哈金的生物合成过程中，至少存在三种形式：一种形式会迅速加工产生贾拉哈金 - C，一种形式在毒液中不易加工且在体外不易自溶，还有一种次要形式在促使其结构不稳定的条件下易发生自溶。这些不同形式的贾拉哈金的存在增加了毒液结构和功能的复杂性，可能是所有蛇毒的一个共同特征。目前正在研究毒液腺中导致这些贾拉哈金异构体的生物学和生物化学特征。（C）2002年爱思唯尔科学（美国）。版权所有。
The reprolysin subfamily of metalloproteinases includes snake venom metalloproteinases (SVMP) and mammalian disintegrin/metalloproteinase. These proteins are synthesized as zymogens and undergo proteolytic processing resulting in a variety of multifunctional proteins. Jararhagin is a P-III SVMP isolated from the venom of Bothrops jararaca. In crude venom, two forms of jararhagin are typically found, full-length jararhagin and jararhagin-C, a proteolytically processed form of jararhagin that is composed of the disintegrin-like and cysteine-rich domains of jararhagin. To better understand the structural and mechanistic bases for these forms of jararhagin in the venom of B. jararaca and the source of venom complexity in general, we have examined the jararhagin forms isolated from venom and the autolysis of isolated jararhagin under the conditions of varying pH, calcium ion concentration, and reducing agents. From our results, jararhagin isolated from venom appears as two forms: a predominant form that is stable to in vitro autolysis and a minor form that is susceptible to autolysis under a variety of conditions including alkaline pH, low calcium ion concentrations, or reducing agent. The autolysis site for production of jararhagin-C from isolated jararhagin was different from that observed for jararhagin-C as isolated from crude venom. Taken together, these data lead us to the conclusion that during the biosynthesis of jararhagin in the venom gland at least three forms are present: one form which is rapidly processed to give rise to jararhagin-C, one form which is resistant to processing in the venom and autolysis in vitro, and one minor form which is susceptible to autolysis under conditions that promote destabilization of its structure. The presence of these different forms of jararhagin contributes to greater structural and functional complexity of the venom and may be a common feature among all snake venoms. The biological and biochemical features in the venom gland responsible for these jararhagin isoforms are currently under investigation. (C) 2002 Elsevier Science (USA). All rights reserved.