Group of Animal Innate Immunity, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China.
Biochem Biophys Res Commun. 2012 Dec 7;429(1-2):111-6. doi: 10.1016/j.bbrc.2012.10.065. Epub 2012 Oct 24.
Scorpion γ-KTx toxins are important molecular tools for studying physiological and pharmacological functions of human ether-á-go-go related gene (hERG) K(+) channels. To pinpoint functional residues of this class of toxins involved in channel binding, we employed a combined approach that integrates evolutionary information and site-directed mutagenesis. Among three positively selected sites (PSSs) identified here, two (Gln18 and Met35) were found to be associated with the toxin's function because their changes significantly decreased the potency of ErgTx1 (also called CnErg1) on hERG1 channel. On the contrary, no potency alteration was observed at the third PSS (Ala42) when the mutation was introduced, which could be due to its location far from the functional surface of the toxin. Our strategy will accelerate the research of structure-function relationship of scorpion K(+) channel toxins.
蝎类γ-KTx 毒素是研究人类醚-α--go-go 相关基因 (hERG) K(+) 通道生理和药理学功能的重要分子工具。为了确定这类毒素中与通道结合相关的功能残基，我们采用了一种整合进化信息和定点突变的综合方法。在本研究中鉴定的三个正选择位点 (PSS) 中，有两个 (Gln18 和 Met35) 与毒素的功能相关，因为它们的变化显著降低了 ErgTx1（也称为 CnErg1）对 hERG1 通道的效力。相反，当引入突变时，第三个 PSS（Ala42）没有观察到效力改变，这可能是由于其位置远离毒素的功能表面。我们的策略将加速蝎类 K(+) 通道毒素结构-功能关系的研究。
