Novel families of toxin-like peptides in insects and mammals: A computational approach
Novel families of toxin-like peptides in insects and mammals: A computational approach
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DOI：
10.1016/j.jmb.2007.02.106
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发表时间：
2007-06-01
影响因子：
5.6
通讯作者：
Linial, Michal
中科院分区：
文献类型：
--
作者：
Kaplan, Noarn;Morpurgo, Noa;Linial, Michal
大多数动物毒素是出现在毒液中的短蛋白质，其序列、结构和功能各不相同。许多这类毒素的一个共同特征是它们的表观结构稳定性。已经报道了在非毒液环境中起作用的内源性毒素样蛋白的零星实例。我们利用机器学习方法，基于序列衍生的特征，并以结构稳定性的概念为指导，对毒素和毒素样蛋白进行大规模搜索。应用该方法对昆虫和哺乳动物的序列揭示了新的毒素样蛋白家族。这些蛋白质之一显示出与在锥蜗牛和猎蝽毒液中表达的离子通道抑制剂的显著相似性，并且令人惊讶地在蜜蜂脑中表达。一项毒性试验中，将该蛋白质注射到鱼中，诱导了强烈但可逆的麻痹作用。我们认为，该蛋白质可能作为一个内源性调节器的电压门控钙通道。此外，我们已经确定了一个新的哺乳动物集群的毒素样蛋白，在睾丸中表达。我们认为，这些蛋白质可能参与调控烟碱乙酰胆碱受体，影响顶体反应和精子活力。最后，我们强调了毒液毒素和抗菌蛋白之间可能的进化联系。我们希望我们的方法能够促进更多新蛋白质家族的发现。(C)2007爱思唯尔有限公司保留所有权利。
Most animal toxins are short proteins that appear in venom and vary in sequence, structure and function. A common characteristic of many such toxins is their apparent structural stability. Sporadic instances of endogenous toxin-like proteins that function in non-venom context have been reported. We have utilized machine learning methodology, based on sequence-derived features and guided by the notion of structural stability, in order to conduct a large-scale search for toxin and toxin-like proteins. Application of the method to insect and mammalian sequences revealed novel families of toxin-like proteins. One of these proteins shows significant similarity to ion channel inhibitors that are expressed in cone snail and assassin bug venom, and is surprisingly expressed in the bee brain. A toxicity assay in which the protein was injected to fish induced a strong yet reversible paralytic effect. We suggest that the protein may function as an endogenous modulator of voltage-gated Ca2+ channels. Additionally, we have identified a novel mammalian cluster of toxin-like proteins that are expressed in the testis. We suggest that these proteins might be involved in regulation of nicotinic acetylcholine receptors that affect the acrosome reaction and sperm motility. Finally, we highlight a possible evolutionary link between venom toxins and antibacterial proteins. We expect our methodology to enhance the discovery of additional novel protein families. (C) 2007 Elsevier Ltd. All rights reserved.