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Molecules 2018, 23(6), 1489; https://doi.org/10.3390/molecules23061489

Mouse β-Defensin 3, A Defensin Inhibitor of Both Its Endogenous and Exogenous Potassium Channels

1
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China
2
Biodrug Research Center, Wuhan University, Wuhan 430072, China
*
Author to whom correspondence should be addressed.
Received: 6 May 2018 / Revised: 9 June 2018 / Accepted: 11 June 2018 / Published: 20 June 2018
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Abstract

The human defensins are recently discovered to inhibit potassium channels, which are classical targets of the animal toxins. Whether other vertebrate defensins are potassium channel inhibitors remains unknown. In this work, we reported that the mouse β-defensin 3 (mBD3) was a novel inhibitor of both endogenous and exogenous potassium channels. The structural analysis showed that mBD3 is the most identical to human Kv1.3 channel-sensitive human β-defensin 2 (hBD2). However, the pharmacological profiles indicated that the recombinant mBD3 (rmBD3) weakly inhibited the mouse and human Kv1.3 channels. Different from the pharmacological features of human β-defensins, mBD3 more selectively inhibited the mouse Kv1.6 and human KCNQ1/KCNE1 channels with IC50 values of 0.6 ± 0.4 μM and 1.2 ± 0.8 μM, respectively. The site directed mutagenesis experiments indicated that the extracellular pore region of mouse Kv1.6 channel was the interaction site of rmBD3. In addition, the minor effect on the channel conductance-voltage relationship curves implied that mBD3 might bind the extracellular transmembrane helices S1-S2 linker and/or S3-S4 linker of mouse Kv1.6 channel. Together, these findings not only revealed mBD3 as a novel inhibitor of both endogenous and exogenous potassium channels, but also provided a clue to investigate the role of mBD3-Kv1.6 channel interaction in the physiological and pathological field in the future. View Full-Text
Keywords: potassium channel; vertebrate defensin; mouse β-defensin 3; pharmacological feature; mouse Kv1.6 channel; inhibitor potassium channel; vertebrate defensin; mouse β-defensin 3; pharmacological feature; mouse Kv1.6 channel; inhibitor
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Zhang, Y.; Zhao, Y.; Liu, H.; Yu, W.; Yang, F.; Li, W.; Cao, Z.; Wu, Y. Mouse β-Defensin 3, A Defensin Inhibitor of Both Its Endogenous and Exogenous Potassium Channels. Molecules 2018, 23, 1489.

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