Isolation and characterization of hainantoxin-IV, a novel antagonist of tetrodotoxin-sensitive sodium channels from the Chinese bird spider Selenocosmia hainana.
A neurotoxin, named hainantoxin-IV, was purified from the venom of the spider Selenocosmia hainana. The amino acid sequence was determined by Edman degradation, revealing it to be a 35-residue polypeptide amidated at its C terminal and including three disulfide bridges: Cys2-Cys17, Cys9-Cys24, and Cys16-Cys31 assigned by partial reduction and sequence analysis. Hainantoxin-IV shares 80% sequence identity with huwentoxin-IV from the spider S. huwena, a potent antagonist that acts at site 1 on tetrodotoxin-sensitive (TTX-S) sodium channels, suggesting that hainantoxin-IV adopts an inhibitor cystine knot structural motif like huwentoin-IV. Under whole-cell voltage-clamp conditions, this toxin has no effect on tetrodotoxin-resistant voltage-gated sodium channels in adult rat dorsal root ganglion neurons, while it blocks TTX-S sodium channels in a manner similar to huwentoxin-IV, and the actions of both toxins on sodium currents are very similar to that of tetrodotoxin. Thus, they define a new family of spider toxins affecting sodium channels.
Liu
Z
Z
College of Life Sciences, Hunan Normal University, Changsha 410081 Hunan, China.
Dai
J
J
Chen
Z
Z
Hu
W
W
Xiao
Y
Y
Liang
S
S
D000595:Amino Acid Sequence; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D026941:Sodium Channel Blockers / Q000302:isolation & purification* / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology; D013111:Spider Venoms / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013112:Spiders; D013779:Tetrodotoxin / Q000494:pharmacology*
D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013111:Spider Venoms; C474037:hainantoxin-IV, Seleconosmia hainana; D013779:Tetrodotoxin