title: Discovery of three toxin peptides with Kv1.3 channel and IL-2 cytokine-inhibiting activities from Non-Buthidae scorpions, Chaerilus tricostatus and Chaerilus tryznai.
abstract: Non-Buthidae venomous scorpions are huge natural sources of toxin peptides; however, only a few studies have been done to understand their toxin peptides. Herein, we describe 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 the 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 toward 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, C. tricostatus and C. tryznai, and highlighted that non-Buthidae venomous scorpions are new natural toxin peptide sources.
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, College of Basic Medicine, Hubei University of Medicine, Hubei, China; Department of Clinical Laboratory, Dongfeng Hospital, Hubei University of Medicine, Hubei, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory, Shiyan Occupational Disease Hospital, Hubei, China.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Hao
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, College of Basic Medicine, Hubei University of Medicine, Hubei, China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, College of Basic Medicine, Hubei University of Medicine, Hubei, China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, College of Basic Medicine, Hubei University of Medicine, Hubei, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Hu
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, College of Basic Medicine, Hubei University of Medicine, Hubei, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, College of Basic Medicine, Hubei University of Medicine, Hubei, China.
authors.forename: Yaru
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei, China.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Li
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei, China.
authors.forename: Yingliang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, College of Basic Medicine, Hubei University of Medicine, Hubei, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, College of Basic Medicine, Hubei University of Medicine, Hubei, China; Department of Clinical Laboratory, Dongfeng Hospital, Hubei University of Medicine, Hubei, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, College of Basic Medicine, Hubei University of Medicine, Hubei, China; Department of Clinical Laboratory, Dongfeng Hospital, Hubei University of Medicine, Hubei, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, College of Basic Medicine, Hubei University of Medicine, Hubei, China; Department of Clinical Laboratory, Dongfeng Hospital, Hubei University of Medicine, Hubei, China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, College of Basic Medicine, Hubei University of Medicine, Hubei, China. Electronic address: chenzy2005@126.com.
authors.forename: Zongyun
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000037:antagonists & inhibitors*; D051657:KCNQ1 Potassium Channel / Q000037:antagonists & inhibitors; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors*; D008297:Male; D008958:Models, Molecular; D062553:NAV1.4 Voltage-Gated Sodium Channel / Q000737:chemistry; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000302:isolation & purification / Q000494:pharmacology; D012604:Scorpion Venoms / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D012605:Scorpions / Q000737:chemistry* / Q000235:genetics; D013601:T-Lymphocytes / Q000737:chemistry
chemical_list: D007376:Interleukin-2; D051657:KCNQ1 Potassium Channel; D051664:Kv1.3 Potassium Channel; D062553:NAV1.4 Voltage-Gated Sodium Channel; D010455:Peptides; D026902:Potassium Channel Blockers; D012604:Scorpion Venoms
keywords: Chaerilidae; IL-2; Kv1.3 channel; Potential immunoregulatory peptide; Scorpion toxin