Centipede KCNQ Inhibitor SsTx Also Targets K_V1.3

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 K_V1.3 channel, which would amplify the broad-spectrum disruptive effect of blocking K_V7 channels. Interestingly, residue R12 in SsTx extends into the selectivity filter to block K_V7.4, however, residue K11 in SsTx replaces this ploy when toxin binds on K_V1.3. Both SsTx and its mutant SsTx_R12A inhibit cytokines production in T cells without affecting the level of K_V1.3 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.