title: Identification of a new specific Kv1.3 channel blocker, Ctri9577, from the scorpion Chaerilus tricostatus.
abstract: Scorpion toxins are valuable resources for discovering new ion channel modulators and drug candidates. Potassium channel Kv1.3 is an important pharmacological target of T cell-mediated autoimmune diseases, which are encouraging the screening and design of the specific peptide blockers for Kv1.3 channel. Ctri9577, the first neurotoxin gene of Chaerilidae family was cloned from the venom of the scorpion Chaerilus tricostatus through the constructing its cDNA library. The sequence analysis showed that the mature peptide of Ctri9577 contained 39 amino acid residues including six conserved cysteines, whose low sequence similarity indicated that it was a new member of α-KTx15 subfamily. By using expression and purification technology, the recombinant peptide was obtained. Subsequently, the electrophysiological experiments indicated that the Ctri9577 peptide selectively inhibited Kv1.3 channel current with an IC(50) of 0.49±0.45 nM without effectively blocking potassium channels Kv1.1, Kv1.2, hERG and SK3. All these findings not only enrich the knowledge of toxins from the Chaerilidae family, but also present a novel potential drug candidate targeting Kv1.3 channels for the therapy of autoimmune diseases.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, People's Republic of China.
authors.forename: Shujun
authors.initials: S
authors.lastname: Xie
authors.forename: Jing
authors.initials: J
authors.lastname: Feng
authors.forename: Congya
authors.initials: C
authors.lastname: Yu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.forename: Yingliang
authors.initials: Y
authors.lastname: Wu
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Cao
authors.forename: Wenxin
authors.initials: W
authors.lastname: Li
authors.forename: Xiaohua
authors.initials: X
authors.lastname: He
authors.forename: Ming
authors.initials: M
authors.lastname: Xiang
authors.forename: Song
authors.initials: S
authors.lastname: Han
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors*; D008564:Membrane Potentials / Q000187:drug effects; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D018408:Patch-Clamp Techniques; D010802:Phylogeny; D026902:Potassium Channel Blockers / Q000302:isolation & purification / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D012346:RNA, Transfer, Amino Acyl; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D012604:Scorpion Venoms / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D012605:Scorpions / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: C575416:Ctri9577 protein, Chaerilus tricostatus; D051664:Kv1.3 Potassium Channel; D026902:Potassium Channel Blockers; D012346:RNA, Transfer, Amino Acyl; D011994:Recombinant Proteins; D012604:Scorpion Venoms