Solution structure and functional characterization of jingzhaotoxin-XI: a novel gating modifier of both potassium and sodium channels.
JZTX-XI is a peptide toxin isolated from the venom of the Chinese spider Chilobrachys jingzhao. It contains 34 residues including six cysteine residues with disulfide bridges linked in the pattern of I-IV, II-V, and III-VI. Using 3'- and 5'-RACE methods, the full-length cDNA was identified as encoding an 86-residue precursor of JZTX-XI. In the electrophysiological assay, JZTX-XI shows activity toward the Kv2.1 channel in a way similar to hanatoxin1 and SGTx1 that both the activation and the deactivation processes are affected, which is in accordance with the high sequence homology among them (over 60% identity). On the other hand, JZTX-XI also exhibits specific interaction against the Nav channels of rat cardiac myocytes with a significant reduction in the peak current and slowing of channel inactivation. The solution structure of native JZTX-XI was determined by 1H NMR methods to identify the structural basis of these specific activities. Structural comparison of JZTX-XI with other gating modifier toxins shows that they all adopt a similar surface profile, a hydrophobic patch surrounded by charged residues such as Arg or Lys, which might be a common structural factor responsible for toxin-channel interaction. JZTX-XI might be an ideal tool to further investigate how spider toxins recognize various ion channels as their targets.
Liao
Zhi
Z
College of Life Sciences, Peking University, Beijing 100083, China.
Yuan
Chunhua
C
Deng
Meichun
M
Li
Jiang
J
Chen
Jinjun
J
Yang
Yuejun
Y
Hu
Weijun
W
Liang
Songping
S
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018360:Crystallography, X-Ray; D018076:DNA, Complementary / Q000302:isolation & purification; D005260:Female; D015640:Ion Channel Gating / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D009498:Neurotoxins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000633:toxicity; D009865:Oocytes / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D010526:Periplaneta; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D015222:Sodium Channels / Q000378:metabolism*; D013111:Spider Venoms / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000633:toxicity; D014982:Xenopus laevis
D018076:DNA, Complementary; D009479:Neuropeptides; D009498:Neurotoxins; D010455:Peptides; D024642:Potassium Channels, Voltage-Gated; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013111:Spider Venoms; C525630:jingzhaotoxin XI, Chilobrachys jingzhao