Scorpion neurotoxins: structure/function relationships and application in agriculture

Continued use of non-specific chemical insecticides poses potential risks t o the environment and to human health resulting from non-target toxicity an d increased insect resistance to these agents, Scorpions produce anti-insec t selective polypeptide toxins that bind to and modulate voltage-sensitive ion channels in excitable tissues, thus offering alternative, environmental ly safer means for insect pest control. Despite this potential, little is k nown about their structural elements dictating anti-insect preference, whic h may be useful for the design of selective insecticides. We used a bacteri al system for expression and genetic dissection of two pharmacologically di stinct scorpion toxins: alpha and excitatory. By exploiting a multi-discipl inary. approach consisting of mutagenesis, protein chemistry, electrophysio logy, binding and toxicity assays, and structural studies, we elucidated th e bioactive surface of two anti-insect toxins, Lqh alpha IT and Bj-xtrIT, I n both polypeptides the bioactive surface is composed of residues surroundi ng the C-terminal region. In addition, a direct, immediate approach in usin g the toxin genes was demonstrated by engineering baculoviruses with cDNAs encoding LqhIT2 (depressant toxin), and LqhIT1 (excitatory toxin) resulting in viral vectors with significantly improved insecticidal efficacy. (C) 20 00 Society of Chemical Industry.