title: Plectasin, first animal toxin-like fungal defensin blocking potassium channels through recognizing channel pore region.
abstract: The potassium channels were recently found to be inhibited by animal toxin-like human β-defensin 2 (hBD2), the first defensin blocker of potassium channels. Whether there are other defensin blockers from different organisms remains an open question. Here, we reported the potassium channel-blocking plectasin, the first defensin blocker from a fungus. Based on the similar cysteine-stabilized alpha-beta (CSαβ) structure between plectasin and scorpion toxins acting on potassium channels, we found that plectasin could dose-dependently block Kv1.3 channel currents through electrophysiological experiments. Besides Kv1.3 channel, plectasin could less inhibit Kv1.1, Kv1.2, IKCa, SKCa3, hERG and KCNQ channels at the concentration of 1 μΜ. Using mutagenesis and channel activation experiments, we found that outer pore region of Kv1.3 channel was the binding site of plectasin, which is similar to the interacting site of Kv1.3 channel recognized by animal toxin blockers. Together, these findings not only highlight the novel function of plectasin as a potassium channel inhibitor, but also imply that defensins from different organisms functionally evolve to be a novel kind of potassium channel inhibitors.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China. xiangfang2012@126.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China. zlxie@whu.edu.cn.
authors.forename: Zili
authors.initials: Z
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China. jfeng@whu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China. weishanyang@whu.edu.cn.
authors.forename: Weishan
authors.initials: W
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China. zjcao@whu.edu.cn.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China. wxli@whu.edu.cn.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Li
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China. zjcao@whu.edu.cn.
authors.forename: Zongyun
authors.initials: Z
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China. ylwu@whu.edu.cn.
authors.forename: Yingliang
authors.initials: Y
authors.lastname: Wu
mesh_terms: D023082:Defensins / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D009183:Mycotoxins / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology*
chemical_list: D023082:Defensins; D009183:Mycotoxins; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C504857:plectasin