College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China.
Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China.
Toxins (Basel). 2019 Feb 1;11(2):76. doi: 10.3390/toxins11020076.
It was recently discovered that Ssm Spooky Toxin (SsTx) with 53 residues serves as a key killer factor in red-headed centipede's venom arsenal, due to its potent blockage of the widely expressed KCNQ channels to simultaneously and efficiently disrupt cardiovascular, respiratory, muscular, and nervous systems, suggesting that SsTx is a basic compound for centipedes' defense and predation. Here, we show that SsTx also inhibits K1.3 channel, which would amplify the broad-spectrum disruptive effect of blocking K7 channels. Interestingly, residue R12 in SsTx extends into the selectivity filter to block K7.4, however, residue K11 in SsTx replaces this ploy when toxin binds on K1.3. Both SsTx and its mutant SsTx_R12A inhibit cytokines production in T cells without affecting the level of K1.3 expression. The results further suggest that SsTx is a key molecule for defense and predation in the centipedes' venoms and it evolves efficient strategy to disturb multiple physiological targets.
最近发现，红头蜈蚣毒液武器库中的 Ssm Spooky Toxin（SsTx）具有 53 个残基，是一种关键的杀伤因子，因为它能够强烈阻断广泛表达的 KCNQ 通道，从而同时有效地破坏心血管、呼吸、肌肉和神经系统，这表明 SsTx 是蜈蚣防御和捕食的基本化合物。在这里，我们表明 SsTx 还抑制 K1.3 通道，这会放大阻断 K7 通道的广谱破坏作用。有趣的是，SsTx 中的残基 R12 延伸到选择性过滤器以阻断 K7.4，然而，当毒素结合到 K1.3 上时，SsTx 中的残基 K11 取代了这种策略。SsTx 和其突变体 SsTx_R12A 都抑制 T 细胞中的细胞因子产生，而不影响 K1.3 表达水平。结果进一步表明，SsTx 是蜈蚣毒液防御和捕食的关键分子，它进化出了有效的策略来干扰多个生理靶标。
