Centipede KCNQ Inhibitor SsTx Also Targets K<sub>V</sub>1.3

oleh: Canwei Du, Jiameng Li, Zicheng Shao, James Mwangi, Runjia Xu, Huiwen Tian, Guoxiang Mo, Ren Lai, Shilong Yang

Format: Article
Diterbitkan: MDPI AG 2019-02-01

Deskripsi

It was recently discovered that Ssm Spooky Toxin (SsTx) with 53 residues serves as a key killer factor in red-headed centipede&#8217;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&#8217; defense and predation. Here, we show that SsTx also inhibits K<sub>V</sub>1.3 channel, which would amplify the broad-spectrum disruptive effect of blocking K<sub>V</sub>7 channels. Interestingly, residue R12 in SsTx extends into the selectivity filter to block K<sub>V</sub>7.4, however, residue K11 in SsTx replaces this ploy when toxin binds on K<sub>V</sub>1.3. Both SsTx and its mutant SsTx_R12A inhibit cytokines production in T cells without affecting the level of K<sub>V</sub>1.3 expression. The results further suggest that SsTx is a key molecule for defense and predation in the centipedes&#8217; venoms and it evolves efficient strategy to disturb multiple physiological targets.