Plectasin, First Animal Toxin-Like Fungal Defensin Blocking Potassium Channels through Recognizing Channel Pore Region
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 p...
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doaj-df430f17cde944e1aa8c16a9773706042020-11-24T21:39:36ZengMDPI AGToxins2072-66512015-01-0171344210.3390/toxins7010034toxins7010034Plectasin, First Animal Toxin-Like Fungal Defensin Blocking Potassium Channels through Recognizing Channel Pore RegionFang Xiang0Zili Xie1Jing Feng2Weishan Yang3Zhijian Cao4Wenxin Li5Zongyun Chen6Yingliang Wu7State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, ChinaState Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, ChinaState Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, ChinaState Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, ChinaState Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, ChinaState Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, ChinaState Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, ChinaState Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, ChinaThe 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.http://www.mdpi.com/2072-6651/7/1/34plectasindefensinpotassium channelsKv1.3 channelmolecular mechanismfunctional evolution |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fang Xiang Zili Xie Jing Feng Weishan Yang Zhijian Cao Wenxin Li Zongyun Chen Yingliang Wu |
spellingShingle |
Fang Xiang Zili Xie Jing Feng Weishan Yang Zhijian Cao Wenxin Li Zongyun Chen Yingliang Wu Plectasin, First Animal Toxin-Like Fungal Defensin Blocking Potassium Channels through Recognizing Channel Pore Region Toxins plectasin defensin potassium channels Kv1.3 channel molecular mechanism functional evolution |
author_facet |
Fang Xiang Zili Xie Jing Feng Weishan Yang Zhijian Cao Wenxin Li Zongyun Chen Yingliang Wu |
author_sort |
Fang Xiang |
title |
Plectasin, First Animal Toxin-Like Fungal Defensin Blocking Potassium Channels through Recognizing Channel Pore Region |
title_short |
Plectasin, First Animal Toxin-Like Fungal Defensin Blocking Potassium Channels through Recognizing Channel Pore Region |
title_full |
Plectasin, First Animal Toxin-Like Fungal Defensin Blocking Potassium Channels through Recognizing Channel Pore Region |
title_fullStr |
Plectasin, First Animal Toxin-Like Fungal Defensin Blocking Potassium Channels through Recognizing Channel Pore Region |
title_full_unstemmed |
Plectasin, First Animal Toxin-Like Fungal Defensin Blocking Potassium Channels through Recognizing Channel Pore Region |
title_sort |
plectasin, first animal toxin-like fungal defensin blocking potassium channels through recognizing channel pore region |
publisher |
MDPI AG |
series |
Toxins |
issn |
2072-6651 |
publishDate |
2015-01-01 |
description |
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. |
topic |
plectasin defensin potassium channels Kv1.3 channel molecular mechanism functional evolution |
url |
http://www.mdpi.com/2072-6651/7/1/34 |
work_keys_str_mv |
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