摘要：
Jingzhaotoxin-XI (JZTX-XI) is a 34-residue peptide from the Chinese tarantula Chilobrachys jingzhao venom that potently inhibits both voltage-gated sodium channel Nav1.5 and voltage-gated potassium channel Kv2.1. In the present study, we further showed that JZTX-XI blocked Kv2.1 currents with the 1050 value of 0.39 +/- 0.06 M. JZTX-XI significantly shifted the current-voltage (I V) curves and normalized conductance-voltage (G V) curves of Kv2.1 channel to more depolarized voltages. Ala-scanning mutagenesis analyses demonstrated that mutants 1273A, F274A, and E277A reduced toxin binding affinity by 10-, 16-, and 18-fold, respectively, suggesting that three common residues (1273, F274, E277) in the Kv2.1 S3b segment contribute to the formation of JZTX-XI receptor site, and the acidic residue Glu at the position 277 in Kv2.1 is the most important residue for JZTX-XI sensitivity. A single replacement of E277 with Asp(D) increased toxin inhibitory activity. These results establish that JZTX-XI inhibits Kv2.1 activation by trapping the voltage sensor in the rested state through a similar mechanism to that of HaTxl, but these two toxins have small differences in the most crucial molecular determinant. Furthermore, the in-depth investigation of the subtle differences in molecular determinants may be useful for increasing our understanding of the molecular details regarding toxin-channel interactions. (C) 2016 Elsevier Ltd. All rights reserved.
作者机构：
[伍兵] School of Biosafely Science and Technology, Hunan Agricultural University, Changsha 410128, China;[周赛男; 申可佳; 谭周进] School of Preclinical Medicine, Hunan University of Chinese Medcine, Changsha 410208, China;[谢丙炎] Institute of Vegetable and Flower, China Academy of Agricultural Sciences, Beijing 100081, China;[孙会强] School of Biosafely Science and Technology, Hunan Agricultural University, Changsha 410128, China, School of Preclinical Medicine, Hunan University of Chinese Medcine, Changsha 410208, China
通讯机构：
[Tan, Z.] S;School of Preclinical Medicine, , Changsha 410208, China
