caa a22 4500 606176608 CHVBK 20210128100748.0 cr unu---uuuuu 210128e20150201xx s 000 0 eng 10.1007/s00018-014-1715-z doi (NATIONALLICENCE)springer-10.1007/s00018-014-1715-z Endogenous animal toxin-like human β-defensin 2 inhibits own K+ channels through interaction with channel extracellular pore region [Elektronische Daten] [Weishan Yang, Jing Feng, Fang Xiang, Zili Xie, Guoyi Zhang, Jean-Marc Sabatier, Zhijian Cao, Wenxin Li, Zongyun Chen, Yingliang Wu] 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. Springer Basel, 2014 Antibacterial and antiviral peptide nationallicence Endogenous inhibitors nationallicence Lymphocyte nationallicence Interaction mechanism nationallicence Cytokine secretion nationallicence Adaptive immune modulation nationallicence Yang Weishan State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 430072, Wuhan, China aut Feng Jing State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 430072, Wuhan, China aut Xiang Fang State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 430072, Wuhan, China aut Xie Zili State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 430072, Wuhan, China aut Zhang Guoyi Institute of Dermatology, Chinese Academy of Medicine Sciences, 210042, Nanjing, China aut Sabatier Jean-Marc Laboratoire INSERM UMR 1097, Université d'Aix-Marseille, 163, Avenue de Luminy, Case 939, TPR2 INSERM, 13288, Marseille Cedex 09, France aut Cao Zhijian State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 430072, Wuhan, China aut Li Wenxin State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 430072, Wuhan, China aut Chen Zongyun State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 430072, Wuhan, China aut Wu Yingliang State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 430072, Wuhan, China aut Cellular and Molecular Life Sciences Springer Basel 72/4(2015-02-01), 845-853 1420-682X 72:4<845 2015 72 18 https://doi.org/10.1007/s00018-014-1715-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-014-1715-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yang Weishan State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 430072, Wuhan, China aut NATIONALLICENCE 700 1- Feng Jing State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 430072, Wuhan, China aut NATIONALLICENCE 700 1- Xiang Fang State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 430072, Wuhan, China aut NATIONALLICENCE 700 1- Xie Zili State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 430072, Wuhan, China aut NATIONALLICENCE 700 1- Zhang Guoyi Institute of Dermatology, Chinese Academy of Medicine Sciences, 210042, Nanjing, China aut NATIONALLICENCE 700 1- Sabatier Jean-Marc Laboratoire INSERM UMR 1097, Université d'Aix-Marseille, 163, Avenue de Luminy, Case 939, TPR2 INSERM, 13288, Marseille Cedex 09, France aut NATIONALLICENCE 700 1- Cao Zhijian State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 430072, Wuhan, China aut NATIONALLICENCE 700 1- Li Wenxin State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 430072, Wuhan, China aut NATIONALLICENCE 700 1- Chen Zongyun State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 430072, Wuhan, China aut NATIONALLICENCE 700 1- Wu Yingliang State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 430072, Wuhan, China aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/4(2015-02-01), 845-853 1420-682X 72:4<845 2015 72 18