Jingzhaotoxin-I, a novel spider neurotoxin preferentially inhibiting cardiac sodium channel inactivation.
Jingzhaotoxin-I (JZTX-I), a 33-residue polypeptide, is derived from the Chinese tarantula Chilobrachys jing-zhao venom based on its ability to evidently increase the strength and the rate of vertebrate heartbeats. The toxin has three disulfide bonds with the linkage of I-IV, II-V, and III-VI that is a typical pattern found in inhibitor cystine knot molecules. Its cDNA determined by rapid amplification of 3'- and 5'-cDNA ends encoded a 62-residue precursor with a small proregion of eight residues. Whole-cell configuration indicated that JZTX-I was a novel neurotoxin preferentially inhibiting cardiac sodium channel inactivation by binding to receptor site 3. Although JZTX-I also exhibits the interaction with channel isoforms expressing in mammalian and insect sensory neurons, its affinity for tetrodotoxin-resistant subtype in mammalian cardiac myocytes (IC50 = 31.6 nm) is approximately 30-fold higher than that for tetrodotoxin-sensitive subtypes in latter tissues. Not affecting outward delay-rectified potassium channels expressed in Xenopus laevis oocytes and tetrodotoxin-resistant sodium channels in mammal sensory neurons, JZTX-I hopefully represents a potent ligand to discriminate cardiac sodium channels from neuronal tetrodotoxin-resistant isoforms. Furthermore, different from any reported spider toxins, the toxin neither modifies the current-voltage relationships nor shifts the steady-state inactivation of sodium channels. Therefore, JZTX-I defines a new subclass of spider sodium channel toxins. JZTX-I is an alpha-like toxin first reported from spider venoms. The result provides an important witness for a convergent functional evolution between spider and other animal venoms.
Xiao
Yucheng
Y
College of Life Sciences, Hunan Normal University, Changsha 410081, China.
Tang
Jianzhou
J
Hu
Weijun
W
Xie
Jinyun
J
Maertens
Chantal
C
Tytgat
Jan
J
Liang
Songping
S
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D019143:Evolution, Molecular; D005260:Female; D020128:Inhibitory Concentration 50; D007313:Insecta; D008024:Ligands; D008297:Male; D008564:Membrane Potentials; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000737:chemistry; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D010802:Phylogeny; D015221:Potassium Channels / Q000737:chemistry; D020033:Protein Isoforms; D051381:Rats; D017207:Rats, Sprague-Dawley; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D015222:Sodium Channels / Q000737:chemistry* / Q000378:metabolism; D013111:Spider Venoms / Q000737:chemistry* / Q000494:pharmacology; D013112:Spiders; D013779:Tetrodotoxin / Q000737:chemistry; D013997:Time Factors; D014982:Xenopus laevis
D018076:DNA, Complementary; D004220:Disulfides; D008024:Ligands; D009498:Neurotoxins; D010455:Peptides; D015221:Potassium Channels; D020033:Protein Isoforms; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013111:Spider Venoms; C500354:jingzhaotoxin-I, Chilobrachys jingzhao; D013779:Tetrodotoxin