2. Academic Validation
  3. Centipede KCNQ Inhibitor SsTx Also Targets KV1.3

Centipede KCNQ Inhibitor SsTx Also Targets KV1.3

  • Toxins (Basel). 2019 Feb 1;11(2):76. doi: 10.3390/toxins11020076.
Canwei Du 1,  Jiameng Li 2,  Zicheng Shao 3,  James Mwangi 4 5,  Runjia Xu 6,  Huiwen Tian 7,  Guoxiang Mo 8,  Ren Lai 9 10 11,  Shilong Yang 12 13
Affiliations

Affiliations

  • 1 College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China. ducw1992@163.com.
  • 2 College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China. 2017116055@njau.edu.cn.
  • 3 College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China. 2016116042@njau.edu.cn.
  • 4 Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China. mwangij1124@yahoo.com.
  • 5 University of Chinese Academy of Sciences, Beijing 100009, China. mwangij1124@yahoo.com.
  • 6 College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China. 2016116040@njau.edu.cn.
  • 7 College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China. 2017116051@njau.edu.cn.
  • 8 College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China. mgx@njau.edu.cn.
  • 9 College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China. rlai72@njau.edu.cn.
  • 10 Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China. rlai72@njau.edu.cn.
  • 11 Sino-African Joint Research Center, Chinese Academy of Science, Wuhan 430074, Hubei, China. rlai72@njau.edu.cn.
  • 12 Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China. yangsl@mail.kiz.ac.cn.
  • 13 Sino-African Joint Research Center, Chinese Academy of Science, Wuhan 430074, Hubei, China. yangsl@mail.kiz.ac.cn.
PMID: 30717088 DOI: 10.3390/toxins11020076
Abstract

It was recently discovered that Ssm Spooky Toxin (SsTx) with 53 residues serves as a key killer factor in red-headed centipede's venom arsenal, due to its potent blockage of the widely expressed KCNQ channels to simultaneously and efficiently disrupt cardiovascular, respiratory, muscular, and nervous systems, suggesting that SsTx is a basic compound for centipedes' defense and predation. Here, we show that SsTx also inhibits KV1.3 channel, which would amplify the broad-spectrum disruptive effect of blocking KV7 channels. Interestingly, residue R12 in SsTx extends into the selectivity filter to block KV7.4, however, residue K11 in SsTx replaces this ploy when toxin binds on KV1.3. Both SsTx and its mutant SsTx_R12A inhibit cytokines production in T cells without affecting the level of KV1.3 expression. The results further suggest that SsTx is a key molecule for defense and predation in the centipedes' venoms and it evolves efficient strategy to disturb multiple physiological targets.

Keywords

Centipede; KV1.3; KV7; SsTx; toxin.

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