1. Discovery and characterization of a family of insecticidal neurotoxins with a rare vicinal disulfide bridge
- Author
-
Glenn F. King, Ross Smith, Merlin E.H. Howden, Xiu-hong Wang, Mark Connor, MacDonald J. Christie, Mark W. Maciejewski, and Graham M. Nicholson
- Subjects
Models, Molecular ,Insecticides ,Protein Folding ,Insecta ,Amino Acid Motifs ,Molecular Sequence Data ,Neurotoxins ,Beta sheet ,Spider Venoms ,Venom ,Biochemistry ,Protein Structure, Secondary ,Homology (biology) ,Evolution, Molecular ,Lethal Dose 50 ,Mice ,chemistry.chemical_compound ,Species Specificity ,Structural Biology ,Genetics ,Animals ,Receptors, Cholinergic ,Amino Acid Sequence ,Disulfides ,Binding site ,Nuclear Magnetic Resonance, Biomolecular ,Chromatography, High Pressure Liquid ,Neurons ,Binding Sites ,Chemistry ,Cystine knot ,Protein Structure, Tertiary ,Inhibitor cystine knot ,Sequence Alignment ,Vicinal ,DNA - Abstract
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 biopesticide 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 databases. The three-dimensional structure of one of these toxins reveals an extremely rare vicinal disulfide bridge that we demonstrate to be critical for insecticidal activity. We propose that J-ACTX comprises an ancestral protein fold that we refer to as the disulfide-directed beta-hairpin.
- Published
- 2000