Cellular and Molecular Life Sciences

, Volume 72, Issue 4, pp 845–853

Endogenous animal toxin-like human β-defensin 2 inhibits own K+ channels through interaction with channel extracellular pore region

  • Weishan Yang
  • Jing Feng
  • Fang Xiang
  • Zili Xie
  • Guoyi Zhang
  • Jean-Marc Sabatier
  • Zhijian Cao
  • Wenxin Li
  • Zongyun Chen
  • Yingliang Wu
Research Article

DOI: 10.1007/s00018-014-1715-z

Cite this article as:
Yang, W., Feng, J., Xiang, F. et al. Cell. Mol. Life Sci. (2015) 72: 845. doi:10.1007/s00018-014-1715-z

Abstract

Human potassium channels are widely inhibited by peptide toxins from venomous animals. However, no human endogenous peptide inhibitor has been discovered so far. In this study, we demonstrate for the first time using electrophysiological techniques, that endogenous human β–defensin 2 (hBD2) is able to selectively and dose-dependently inhibit the human voltage-gated Kv1.3 channel at picomolar peptide concentration. The co-immunoprecipitation assays further supported the selective binding of hBD2 to Kv1.3 channel. Using mutagenesis experiments, we found that the outer pore domain of Kv1.3 channel was the binding site of hBD2, which is similar to the interacting site of Kv1.3 channel recognized by animal toxin inhibitors. The hBD2 was able to suppress IL-2 production through inhibition of Kv1.3 channel currents in human Jurkat cells, which was further confirmed by the lack of hBD2 activity on IL-2 production after Kv1.3 knockdown in these cells. More interestingly, hBD2 was also found to efficiently inhibit Kv1.3 channel currents and suppress IL-2 production in both human primary CD3+ T cells and peripheral mononuclear cells from either healthy donors or psoriasis patients. Our findings not only evidenced hBD2 as the first characterized endogenous peptide inhibitor of human potassium channels, but also paved a promising avenue to investigate newly discovered function of hBD2 as Kv1.3 channel inhibitor in the immune system and other fields.

Keywords

Antibacterial and antiviral peptide Endogenous inhibitors Lymphocyte Interaction mechanism Cytokine secretion Adaptive immune modulation 

Supplementary material

18_2014_1715_MOESM1_ESM.doc (2.3 mb)
Supplementary material 1 (DOC 2405 kb)

Copyright information

© Springer Basel 2014

Authors and Affiliations

  • Weishan Yang
    • 1
  • Jing Feng
    • 1
  • Fang Xiang
    • 1
  • Zili Xie
    • 1
  • Guoyi Zhang
    • 3
  • Jean-Marc Sabatier
    • 4
  • Zhijian Cao
    • 1
    • 2
  • Wenxin Li
    • 1
    • 2
  • Zongyun Chen
    • 1
  • Yingliang Wu
    • 1
    • 2
  1. 1.State Key Laboratory of Virology, College of Life SciencesWuhan UniversityWuhanChina
  2. 2.Center for BioDrug ResearchWuhan UniversityWuhanChina
  3. 3.Institute of DermatologyChinese Academy of Medicine SciencesNanjingChina
  4. 4.Laboratoire INSERM UMR 1097Université d’Aix-MarseilleMarseille Cedex 09France

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