PMID- 26721415
OWN - NLM
STAT- MEDLINE
DCOM- 20161101
LR  - 20161230
IS  - 1879-3150 (Electronic)
IS  - 0041-0101 (Linking)
VI  - 111
DP  - 2016 Mar 1
TI  - Molecular determinant for the tarantula toxin Jingzhaotoxin-I slowing the fast 
      inactivation of voltage-gated sodium channels.
PG  - 13-21
LID - S0041-0101(15)30156-2 [pii]
LID - 10.1016/j.toxicon.2015.12.009 [doi]
AB  - Peptide toxins often have divergent pharmacological functions and are powerful 
      tools for a deep review on the current understanding of the structure-function 
      relationships of voltage-gated sodium channels (VGSCs). However, knowing about 
      the interaction of site 3 toxins from tarantula venoms with VGSCs is not 
      sufficient. In the present study, using whole-cell patch clamp technique, we 
      determined the effects of Jingzhaotoxin-I (JZTX-I) on five VGSC subtypes 
      expressed in HEK293 cells. The results showed that JZTX-I could inhibit the 
      inactivation of rNav1.2, rNav1.3, rNav1.4, hNav1.5 and hNav1.7 channels with the 
      IC50 of 870 +/- 8 nM, 845 +/- 4 nM, 339 +/- 5 nM, 335 +/- 9 nM, and 348 +/- 6 nM, 
      respectively. The affinity of the toxin interaction with subtypes (rNav1.4, 
      hNav1.5, and hNav1.7) was only 2-fold higher than that for subtypes (rNav1.2 and 
      rNav1.3). The toxin delayed the inactivation of VGSCs without affecting the 
      activation and steady-state inactivation kinetics in the physiological range of 
      voltages. Site-directed mutagenesis indicated that the toxin interacted with site 
      3 located at the extracellular S3-S4 linker of domain IV, and the acidic residue 
      Asp at the position1609 in hNav1.5 was crucial for JZTX-I activity. Our results 
      provide new insights in single key residue that allows toxins to recognize 
      distinct ion channels with similar potency and enhance our understanding of the 
      structure-function relationships of toxin-channel interactions.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Tao, Huai
AU  - Tao H
AD  - Department of Biochemistry and Molecular Biology, Hunan University of Chinese 
      Medicine, Changsha 410208, Hunan, China; Division of Stem Cell Regulation and 
      Application, Hunan University of Chinese Medicine, Changsha 410208, Hunan, China. 
      Electronic address: taohuai123@126.com.
FAU - Chen, Xia
AU  - Chen X
AD  - Department of Orthopedics, The Second Xiangya Hospital of Central South 
      University, Changsha 410011, Hunan, China.
FAU - Lu, Min
AU  - Lu M
AD  - Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of 
      Education, College of Life Sciences, Hunan Normal University, Changsha 410081, 
      Hunan, China.
FAU - Wu, Yuanyuan
AU  - Wu Y
AD  - Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of 
      Education, College of Life Sciences, Hunan Normal University, Changsha 410081, 
      Hunan, China.
FAU - Deng, Meichun
AU  - Deng M
AD  - State Key Laboratory of Medical Genetics and School of Life Sciences, Central 
      South University, Changsha 410013, Hunan, China.
FAU - Zeng, Xiongzhi
AU  - Zeng X
AD  - Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of 
      Education, College of Life Sciences, Hunan Normal University, Changsha 410081, 
      Hunan, China.
FAU - Liu, Zhonghua
AU  - Liu Z
AD  - Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of 
      Education, College of Life Sciences, Hunan Normal University, Changsha 410081, 
      Hunan, China.
FAU - Liang, Songping
AU  - Liang S
AD  - Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of 
      Education, College of Life Sciences, Hunan Normal University, Changsha 410081, 
      Hunan, China. Electronic address: liangsp@hunnu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151223
PL  - England
TA  - Toxicon
JT  - Toxicon : official journal of the International Society on Toxinology
JID - 1307333
RN  - 0 (Peptides)
RN  - 0 (Spider Venoms)
RN  - 0 (Voltage-Gated Sodium Channel Blockers)
RN  - 0 (Voltage-Gated Sodium Channels)
RN  - 0 (jingzhaotoxin-I, Chilobrachys jingzhao)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - HEK293 Cells
MH  - Humans
MH  - Membrane Potentials/drug effects
MH  - Molecular Sequence Data
MH  - Peptides/chemistry/*pharmacology
MH  - Spider Venoms/chemistry/*pharmacology
MH  - Spiders/*physiology
MH  - Voltage-Gated Sodium Channel Blockers/chemistry/*pharmacology
MH  - Voltage-Gated Sodium Channels/*metabolism
OTO - NOTNLM
OT  - Inactivation
OT  - Jingzhaotoxin-I
OT  - Mutation
OT  - Voltage-gated sodium channels
EDAT- 2016/01/02 06:00
MHDA- 2016/11/02 06:00
CRDT- 2016/01/02 06:00
PHST- 2015/10/20 00:00 [received]
PHST- 2015/11/23 00:00 [revised]
PHST- 2015/12/16 00:00 [accepted]
PHST- 2016/01/02 06:00 [entrez]
PHST- 2016/01/02 06:00 [pubmed]
PHST- 2016/11/02 06:00 [medline]
AID - S0041-0101(15)30156-2 [pii]
AID - 10.1016/j.toxicon.2015.12.009 [doi]
PST - ppublish
SO  - Toxicon. 2016 Mar 1;111:13-21. doi: 10.1016/j.toxicon.2015.12.009. Epub 2015 Dec 
      23.