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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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Binding Sites
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Chromatography, High Pressure Liquid
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Disulfides / chemistry*
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Disulfides / metabolism*
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Evolution, Molecular
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Insecta / cytology
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Insecta / drug effects
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Insecta / metabolism
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Insecticides / chemistry*
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Insecticides / isolation & purification*
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Insecticides / toxicity
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Lethal Dose 50
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Mice
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Models, Molecular
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Molecular Sequence Data
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Neurons / drug effects
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Neurons / metabolism
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Neurotoxins / chemistry*
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Neurotoxins / isolation & purification*
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Neurotoxins / toxicity
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Nuclear Magnetic Resonance, Biomolecular
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Protein Folding
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Receptors, Cholinergic / metabolism
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Sequence Alignment
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Species Specificity
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Spider Venoms / chemistry
Substances
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Disulfides
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Insecticides
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Neurotoxins
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Receptors, Cholinergic
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Spider Venoms