Tian Caihuan, Yuan Yuzhe, Zhu Shunyi
Group of Animal Innate Immunity, State Key Laboratory of Integrated Management of Pest Insects & Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China.
Toxicon. 2008 Mar 15;51(4):555-62. doi: 10.1016/j.toxicon.2007.11.010. Epub 2007 Nov 22.
Scorpion depressant toxins represent a distinct pharmacological group of sodium channel neurotoxins, identified by their preferential ability in induction of depressant and flaccid paralysis of insects. However, recent observations that some members in this group exhibit anti-mammal activity raise an interesting evolutionary question of whether it is a consequence of adaptive evolution to the early radiation of mammals on earth. By employing the maximum likelihood method, we provided convincing statistical evidence in favor of positive selection driving the evolution of the depressant toxins, and found that two of three positively selected sites are located on the functional surface of the toxins. A complex model of the scorpion depressant toxin LqhIT2 binding to insect sodium channel alpha-subunit (DmNav1) was constructed by structural bioinformatics approaches which highlights a possible direct interaction between these two sites and insect sodium channels. Our work presented here thus suggests that accelerated substitutions in these site residues could offer an evolutionary advantage for these toxins to adapt different channels from diverse origins.
蝎类抑制性毒素代表了一类独特的钠通道神经毒素药理学组，其特征在于它们优先诱导昆虫出现抑制性和弛缓性麻痹的能力。然而，最近观察到该组中的一些成员具有抗哺乳动物活性，这引发了一个有趣的进化问题，即这是否是对地球上早期哺乳动物辐射的适应性进化的结果。通过采用最大似然法，我们提供了令人信服的统计证据支持正选择驱动抑制性毒素的进化，并发现三个正选择位点中的两个位于毒素的功能表面上。通过结构生物信息学方法构建了蝎类抑制性毒素LqhIT2与昆虫钠通道α亚基（DmNav1）结合的复杂模型，该模型突出了这两个位点与昆虫钠通道之间可能的直接相互作用。因此，我们在此展示的工作表明，这些位点残基的加速替换可为这些毒素适应来自不同来源的不同通道提供进化优势。
