title: Two recombinant depressant scorpion neurotoxins differentially affecting mammalian sodium channels.
abstract: The scorpion depressant toxins are a group of evolutionarily conserved polypeptides targeting sodium channels, which show preferential ability to induce flaccid paralysis in insects, making them attractive candidates for the construction of transgenic plants or viral vectors to control pests. In this study, two new depressant toxin-like peptides (BmKITc and BmKITc2) differing only at position 52 (Lys for Thr) were produced in Escherichia coli. Circular dichroism analysis indicated that these two recombinant peptides display a typical structural feature similar to native scorpion toxins. They both cause a maintained current component at the last phase of inactivation of the insect sodium channel DmNav1/tipE expressed in Xenopus oocytes and interestingly, they do not produce a beta effect despite of their primary structure as beta-toxins. Furthermore, an inhibitory effect with BmKITc but not with BmKITc2 was observed on TTX-R sodium currents in rat DRG neurons. We hypothesize that such differential potency highlights a crucial role of lysine 52 in channel selectivity. Our results therefore indicate that, in spite of the general idea, not all scorpion depressant toxins interact with mammalian and/or insect sodium channels in the same manner.
authors.affiliation: Group of Animal Innate Immunity, State Key Laboratory of Integrated Management of Pest Insect & Rodents, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing 100101, P.R. China.
authors.forename: Yuzhe
authors.initials: Y
authors.lastname: Yuan
authors.forename: Lan
authors.initials: L
authors.lastname: Luo
authors.forename: Steve
authors.initials: S
authors.lastname: Peigneur
authors.forename: Jan
authors.initials: J
authors.lastname: Tytgat
authors.forename: Shunyi
authors.initials: S
authors.lastname: Zhu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D003001:Cloning, Molecular; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D007313:Insecta / Q000187:drug effects; D008297:Male; D008969:Molecular Sequence Data; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000187:drug effects*; D009498:Neurotoxins / Q000737:chemistry / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011487:Protein Conformation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D012604:Scorpion Venoms / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D016415:Sequence Alignment; D015222:Sodium Channels / Q000187:drug effects*; D013045:Species Specificity; D014982:Xenopus laevis
chemical_list: C550926:BmKITc protein, Mesobuthus martensii; C550927:BmKITc2 protein, Mesobuthus martensii; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D011994:Recombinant Proteins; C568253:Scn2A protein, rat; D012604:Scorpion Venoms; D015222:Sodium Channels