Characterization of scorpion alpha-like toxin group using two new toxins from the scorpion Leiurus quinquestriatus hebraeus.
Two novel toxins, Lqh6 and Lqh7, isolated from the venom of the scorpion Leiurus quinquestriatus hebraeus, have in their sequence a molecular signature (8Q/KPE10) associated with a recently defined group of alpha-toxins that target Na channels, namely the alpha-like toxins [reviewed in Gordon, D., Savarin, P., Gurevitz, M. & Zinn-Justin, S. (1998) J. Toxicol. Toxin Rev. 17, 131-159]. Lqh6 and Lqh7 are highly toxic to insects and mice, and inhibit the binding of alpha-toxins to cockroach neuronal membranes. Although they kill rodents by intracerebroventricular injection, they do not inhibit the binding of antimammal alpha-toxins (e.g. Lqh2) to rat brain synaptosomes, not even at high concentrations. Furthermore, in voltage-clamp experiments, rat brain Na channels IIA (rNav1.2A) expressed in Xenopus oocytes are not affected by Lqh6 nor by Lqh7 below 3 micro m. In contrast, muscular Na channels (rNav1.4 and hNav1.5) expressed in the same cells respond to nanomolar concentrations of Lqh6 and Lqh7 by slowing of Na current inactivation and a leftward shift of the peak conductance-voltage curve. The structural and pharmacological properties of the new toxins are compared to those of other scorpion alpha-toxins in order to re-examine the hallmarks previously set for the alpha-like toxin group.
Hamon
Alain
A
Laboratoire de Neurophysiologie, UPRES EA-2647, Université d'Angers, France.
Gilles
Nicolas
N
Sautière
Pierre
P
Martinage
Arlette
A
Kopeyan
Charles
C
Ulens
Chris
C
Tytgat
Jan
J
Lancelin
Jean-Marc
JM
Gordon
Dalia
D
D000595:Amino Acid Sequence; D000818:Animals; D003058:Cockroaches / Q000187:drug effects; D005260:Female; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D007928:Lethal Dose 50; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000187:drug effects / Q000235:genetics; D018482:Muscle, Skeletal / Q000737:chemistry; D009206:Myocardium / Q000737:chemistry; D062551:NAV1.2 Voltage-Gated Sodium Channel; D062554:NAV1.5 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000187:drug effects; D009498:Neurotoxins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology / Q000633:toxicity; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D011487:Protein Conformation; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000187:drug effects; D012604:Scorpion Venoms / Q000737:chemistry* / Q000145:classification / Q000302:isolation & purification* / Q000494:pharmacology / Q000633:toxicity; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014982:Xenopus laevis
C114938:Lqh II toxin; C114939:Lqh III toxin; C466178:Lqh6 toxin, Leiurus quinquestriatus hebraeus; C466179:Lqh7 toxin, Leiurus quinquestriatus hebraeus; D009124:Muscle Proteins; D062551:NAV1.2 Voltage-Gated Sodium Channel; D062554:NAV1.5 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D011993:Recombinant Fusion Proteins; C568251:SCN2A protein, human; C568320:SCN5A protein, human; C568253:Scn2A protein, rat; C000654500:Scn2a protein, mouse; C466180:Scn4a protein, rat; C568321:Scn5a protein, mouse; C568322:Scn5a protein, rat; D012604:Scorpion Venoms; D015222:Sodium Channels; C029574:scorpion toxin receptor; D012964:Sodium