signature=78d38e18c5078bc4b970f052dabe21e6,Characterization of scorpion alpha-like toxin group using...

摘要：

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 ±-toxins that target Na channels, namely the ±-like toxins [reviewed in Gordon, D., Savarin, P., Gurevitz, M. & Zinn-Justin, S. (1998) J. Toxicol. Toxin Rev . 17 , 131159]. Lqh6 and Lqh7 are highly toxic to insects and mice, and inhibit the binding of ±-toxins to cockroach neuronal membranes. Although they kill rodents by intracerebroventricular injection, they do not inhibit the binding of antimammal ±-toxins (e.g. Lqh2) to rat brain synaptosomes, not even at high concentrations. Furthermore, in voltage-clamp experiments, rat brain Na channels IIA (rNa v 1.2A) expressed in Xenopus oocytes are not affected by Lqh6 nor by Lqh7 below 3 m . In contrast, muscular Na channels (rNa v 1.4 and hNa v 1.5) 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 conductancevoltage curve. The structural and pharmacological properties of the new toxins are compared to those of other scorpion ±-toxins in order to re-examine the hallmarks previously set for the ±-like toxin group.

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