Discovery of three toxin peptides with Kv1.3 channel and IL-2 cytokine inhibiting activities from Non-Buthidae scorpions Chaerilus tricostatus and Chaerilus tryznai

Publication date: Available online 12 March 2017
Source:Peptides
Author(s): Li Ding, Jing Chen, Jinbo Hao, Jiahui Zhang, Xuejun Huang, Fangfang Hu, Zheng Wu, Yaru Liu, Wenxin Li, Zhijian Cao, Yingliang Wu, Jian Li, Shan Li, Hongyan Liu, Wenlong Wu, Zongyun Chen
Non-Buthidae venomous scorpions are huge natural sources, however, only a few works have been done to understand their toxin peptides. Here, we described three new potential immunomodulating toxin peptides Ctri18, Ctry68 and Ctry2908 from two Non-Buthidae scorpions Chaerilus tricostatus and Chaerilus tryznai. Sequence alignment analyses showed that Ctri18, Ctry68 and Ctry2908 are three new members of scorpion toxin α-KTx15 subfamily. Electrophysiological experiments showed that Ctri18, Ctry68 and Ctry2908 blocked the Kv1.3 channel at micromole to nanomole levels, but had weak effects on potassium channel KCNQ1 and sodium channel Nav1.4, which indicated that Ctri18, Ctry68 and Ctry2908 might have specific inhibiting effects on the Kv1.3 channel. ELISA experiments showed that Ctri18, Ctry68 and Ctry2908 inhibited IL-2 cytokine secretions of activated T lymphocyte in human PBMCs. Excitingly, consistent with the good Kv1.3 channel inhibitory activity, Ctry2908 inhibited cytokine IL-2 secretion in nanomole level, which indicated that Ctry2908 might be a new lead drug template towards Kv1.3 channels. Together, these studies discovered three new toxin peptides Ctri18, Ctry68 and Ctry2908 with Kv1.3 channel and IL-2 cytokine inhibiting activities from two scorpions Chaerilus tricostatus and Chaerilus tryznai, and highlighted that non-Buthidae venomous scorpions are new natural toxin peptide sources.



http://ift.tt/2mRjPwz