Solution structure of Jingzhaotoxin-III, a peptide toxin inhibiting both Nav1.5 and Kv2.1 channels

Zhi Liao; Chunhua Yuan; Kuan Peng; Yucheng Xiao; Songping Liang

doi:10.1016/j.toxicon.2007.03.006

Solution structure of Jingzhaotoxin-III, a peptide toxin inhibiting both Nav1.5 and Kv2.1 channels

Toxicon. 2007 Jul;50(1):135-43. doi: 10.1016/j.toxicon.2007.03.006. Epub 2007 Mar 16.

Authors

Zhi Liao¹, Chunhua Yuan, Kuan Peng, Yucheng Xiao, Songping Liang

Affiliation

¹ College of Life Sciences, Peking University, Beijing 100083, PR China.

PMID: 17481690
DOI: 10.1016/j.toxicon.2007.03.006

Abstract

Jingzhaotoxin-III (JZTX-III) is a peptide toxin isolated from the venom of the Chinese spider Chilobrachys jingzhao that inhibits Nav channels of rat cardiac myocytes by modifying voltage-dependent gating and also binds to Kv2.1 channel (Kd = 0.43 microM) with an action model similar to that of hanatoxin1 and SGTx1. The solution structure of JZTX-III was determined by (1)H 2D NMR method. The toxin adopts an ICK motif composed of three beta-strands connected by four turns. Structural comparison of JZTX-III with those of other ICK motif peptides shows that they all adopt a conserved surface profile, a hydrophobic patch surrounded by charged residues, which might be the crucial site for voltage-gating ion channel inhibition. Furthermore, the similar action model of JZTX-III affecting both Kv and Nav channels implies that JZTX-III recognized a conserved receptor within the voltage sensing domains, which is similar to that of hanatoxin1 binding to both Kv and Cav channels.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Motifs
Animals
Arachnida / metabolism*
Female
Hydrophobic and Hydrophilic Interactions
Ion Channel Gating / drug effects
Models, Molecular
NAV1.5 Voltage-Gated Sodium Channel
Nuclear Magnetic Resonance, Biomolecular
Oocytes / metabolism
Peptides / chemistry*
Peptides / isolation & purification
Peptides / toxicity*
Potassium Channel Blockers / chemistry
Potassium Channel Blockers / isolation & purification
Potassium Channel Blockers / pharmacology
Protein Conformation
Rats
Shab Potassium Channels / antagonists & inhibitors*
Sodium Channel Blockers / chemistry
Sodium Channel Blockers / isolation & purification
Sodium Channel Blockers / pharmacology
Sodium Channels / metabolism*
Spider Venoms / chemistry*
Spider Venoms / isolation & purification
Spider Venoms / toxicity*
Structure-Activity Relationship
Xenopus laevis

Substances

Kcnb1 protein, rat
NAV1.5 Voltage-Gated Sodium Channel
Peptides
Potassium Channel Blockers
Scn5a protein, rat
Shab Potassium Channels
Sodium Channel Blockers
Sodium Channels
Spider Venoms
jingzhaotoxin-III, Chilobrachys jingzhao