Discovery and characterization of a family of insecticidal neurotoxins with a rare vicinal disulfide bridge

We have isolated a family of insect-selective neurotoxins from the venom of the Australian funnel-web spider that appear to be good candidates for bio pesticide engineering. These peptides, which we have named the Janus-faced atracotoxins (J-ACTXs), each contain 36 or 37 residues, with four disulfide bridges, and they show no homology to any sequences in the protein/DNA dat abases. The three-dimensional structure of one of these toxins reveals an e xtremely rare vicinal disulfide bridge that we demonstrate to be critical f or insecticidal activity. We propose that J-ACTX comprises an ancestral pro tein fold that we refer to as the disulfide-directed beta-hairpin.