Chinese-scorpion (Buthus martensi Karsch) toxin BmK alphaIV, a novel modulator of sodium channels: from genomic organization to functional analysis.
In the present study, BmK alphaIV, a novel modulator of sodium channels, was cloned from venomous glands of the Chinese scorpion (Buthus martensi Karsch) and expressed successfully in Escherichia coli. The BmK alphaIV gene is composed of two exons separated by a 503 bp intron. The mature polypeptide contains 66 amino acids. BmK alphaIV has potent toxicity in mice and cockroaches. Surface-plasmon-resonance analysis found that BmK alphaIV could bind to both rat cerebrocortical synaptosomes and cockroach neuronal membranes, and shared similar binding sites on sodium channels with classical AaH II (alpha-mammal neurotoxin from the scorpion Androctonus australis Hector), BmK AS (beta-like neurotoxin), BmK IT2 (the depressant insect-selective neurotoxin) and BmK abT (transitional neurotoxin), but not with BmK I (alpha-like neurotoxin). Two-electrode voltage clamp recordings on rNav1.2 channels expressed in Xenopus laevis oocytes revealed that BmK alphaIV increased the peak amplitude and prolonged the inactivation phase of Na+ currents. The structural and pharmacological properties compared with those of other scorpion alpha-toxins suggests that BmK alphaIV represents a novel subgroup or functional hybrid of alpha-toxins and might be an evolutionary intermediate neurotoxin for alpha-toxins.
Chai
Zhi-Fang
ZF
Graduate School of the Chinese Academy of Sciences, Shanghai Institute of Physiology, Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, People's Republic of China.
Zhu
Mang-Mang
MM
Bai
Zhan-Tao
ZT
Liu
Tong
T
Tan
Miao
M
Pang
Xue-Yan
XY
Ji
Yong-Hua
YH
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002462:Cell Membrane / Q000187:drug effects; D002942:Circular Dichroism; D003001:Cloning, Molecular; D003058:Cockroaches / Q000166:cytology / Q000187:drug effects; D019143:Evolution, Molecular; D005260:Female; D005796:Genes; D005822:Genetic Vectors / Q000235:genetics; D017136:Ion Transport / Q000187:drug effects; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D009498:Neurotoxins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000494:pharmacology* / Q000633:toxicity; D009865:Oocytes; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D012604:Scorpion Venoms / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D012605:Scorpions / Q000737:chemistry / Q000235:genetics; D012640:Seizures / Q000139:chemically induced; D016415:Sequence Alignment; D012964:Sodium / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology* / Q000633:toxicity; D015222:Sodium Channels / Q000187:drug effects; D013035:Spasm / Q000139:chemically induced; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013574:Synaptosomes / Q000187:drug effects; D014982:Xenopus laevis
C514521:BmK alpha IV toxin, Buthus martensi Karsch; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D011993:Recombinant Fusion Proteins; C568253:Scn2A protein, rat; C000654500:Scn2a protein, mouse; D012604:Scorpion Venoms; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D012964:Sodium