PMID- 23246579
OWN - NLM
STAT- MEDLINE
DCOM- 20130723
LR  - 20131121
IS  - 1879-3150 (Electronic)
IS  - 0041-0101 (Linking)
VI  - 63
DP  - 2013 Mar 1
TI  - Molecular determinants for the tarantula toxin jingzhaotoxin-I interacting with 
      potassium channel Kv2.1.
PG  - 129-36
LID - S0041-0101(12)00822-7 [pii]
LID - 10.1016/j.toxicon.2012.12.001 [doi]
AB  - With high binding affinity and distinct pharmacological functions, animal toxins 
      are powerful ligands to investigate the structure-function relationships of 
      voltage-gated ion channels. Jingzhaotoxin-I (JZTX-I) is an important neurotoxin 
      from the tarantula Chilobrachys jingzhao venom that inhibits both sodium and 
      potassium channels. In our previous work, JZTX-I, as a gating modifier, is able 
      to inhibit activation of the potassium channel subtype Kv2.1. However, its 
      binding site on Kv2.1 remains unknown. In this study, using Ala-scanning 
      mutagenesis strategy, we demonstrated that four residues (I273, F274, E277, and 
      K280) in S3b-S4 motif contributed to the formation of JZTX-I binding site. The 
      mutations I273A, F274A, E277A, and K280A reduced toxin binding affinity by 6-, 
      10-, 8-, and 7-fold, respectively. Taken together with our previous data that 
      JZTX-I accelerated channel deactivation, these results suggest that JZTX-I 
      inhibits Kv2.1 activation by docking onto the voltage sensor paddle and trapping 
      the voltage sensor in the closed state.
CI  - Copyright (c) 2012. Published by Elsevier Ltd.
FAU - Tao, Huai
AU  - Tao H
AD  - Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of 
      Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan 
      410081, China.
FAU - Wu, Yuanyuan
AU  - Wu Y
FAU - Deng, Meichun
AU  - Deng M
FAU - He, Juan
AU  - He J
FAU - Wang, Meichi
AU  - Wang M
FAU - Xiao, Yucheng
AU  - Xiao Y
FAU - Liang, Songping
AU  - Liang S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121213
PL  - England
TA  - Toxicon
JT  - Toxicon : official journal of the International Society on Toxinology
JID - 1307333
RN  - 0 (Peptides)
RN  - 0 (RNA Caps)
RN  - 0 (Shab Potassium Channels)
RN  - 0 (Spider Venoms)
RN  - 0 (jingzhaotoxin-I, Chilobrachys jingzhao)
RN  - OF5P57N2ZX (Alanine)
SB  - IM
MH  - Alanine/genetics
MH  - Animals
MH  - Binding Sites/drug effects/genetics
MH  - Electric Conductivity
MH  - Female
MH  - Ion Channel Gating/drug effects/physiology
MH  - Membrane Potentials/drug effects
MH  - Models, Molecular
MH  - Mutagenesis
MH  - Oocytes/drug effects/metabolism
MH  - Patch-Clamp Techniques
MH  - Peptides/genetics/*metabolism/toxicity
MH  - Point Mutation
MH  - Protein Binding
MH  - RNA Caps/pharmacology
MH  - Shab Potassium Channels/genetics/*metabolism
MH  - Spider Venoms/genetics/*metabolism/toxicity
MH  - *Spiders
MH  - Xenopus laevis
EDAT- 2012/12/19 06:00
MHDA- 2013/07/24 06:00
CRDT- 2012/12/19 06:00
PHST- 2012/09/14 00:00 [received]
PHST- 2012/12/01 00:00 [revised]
PHST- 2012/12/05 00:00 [accepted]
PHST- 2012/12/19 06:00 [entrez]
PHST- 2012/12/19 06:00 [pubmed]
PHST- 2013/07/24 06:00 [medline]
AID - S0041-0101(12)00822-7 [pii]
AID - 10.1016/j.toxicon.2012.12.001 [doi]
PST - ppublish
SO  - Toxicon. 2013 Mar 1;63:129-36. doi: 10.1016/j.toxicon.2012.12.001. Epub 2012 Dec 
      13.