Jingzhaotoxin-IX, a novel gating modifier of both sodium and potassium channels from Chinese tarantula Chilobrachys jingzhao.
Tarantula Chilobrachys jingzhao is one of the most venomous species distributed in China. In this study, we have isolated and characterized a novel neurotoxin named Jingzhaotoxin-IX (JZTX-IX) from the venom of the tarantula. JZTX-IX is a C-terminally amidated peptide composed of 35 amino acid residues. The toxin shows 74% sequence identity with CcoTx3 from southeastern Africa tarantula Ceratogyrus cornuatus. JZTX-IX was found to interact with multiple types of ion channels including voltage-gated sodium channels (both tetrodotoxin-resistant and tetrodotoxin-sensitive isoforms) and Kv2.1 channel. The toxin had no effect on delayed rectifier potassium channel Kv1.1, 1.2 and 1.3. JZTX-IX shifted the voltage dependence of channel activation to more positive voltages, but binding of toxin to ion channels was not reversible by extreme depolarization. In addition, JZTX-IX could bias the activities of ion channels towards closed state because the time constant for decay (channel deactivation) of tail currents became faster in the presence of toxin. Taken together with the finding that 10 microM JZTX-IX completely blocked ion channels at resting potential without pulsing, we propose that JZTX-IX is a gating modifier showing low selectivity for ion channel types and trapping voltage sensor at closed state.
Deng
Meichun
M
Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Sciences, Hunan Normal University, Hunan, China.
Kuang
Fang
F
Sun
Zhenghua
Z
Tao
Huai
H
Cai
Tianfu
T
Zhong
Luanluan
L
Chen
Zairan
Z
Xiao
Yucheng
Y
Liang
Songping
S
D000818:Animals; D002460:Cell Line; D051668:Delayed Rectifier Potassium Channels / Q000378:metabolism*; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D009474:Neurons / Q000378:metabolism; D009498:Neurotoxins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism* / Q000633:toxicity; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism* / Q000633:toxicity; D010526:Periplaneta; D051381:Rats; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D015222:Sodium Channels / Q000378:metabolism*; D013111:Spider Venoms / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism* / Q000633:toxicity; D013112:Spiders / Q000378:metabolism*; D013779:Tetrodotoxin / Q000633:toxicity; D014982:Xenopus laevis
D051668:Delayed Rectifier Potassium Channels; C546083:Jingzhaotoxin-IX; D009498:Neurotoxins; D010455:Peptides; D015222:Sodium Channels; D013111:Spider Venoms; D013779:Tetrodotoxin