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The structure of a novel insecticidal neurotoxin, ω-atracotoxin-HV1, from the venom of an Australian funnel web spider

Nature Structural Biology volume 4, pages 559–566 (1997)Cite this article

Abstract

A family of potent insecticidal toxins has recently been isolated from the venom of Australian funnel web spiders. Among these is the 37-residue peptide ω-atracotoxin-HV1 (ω-ACTX-HV1) from Hadronyche versuta. We have chemically synthesized and folded ω-ACTX-HV1, shown that it is neurotoxic, ascertained its disulphide bonding pattern, and determined its three-dimensional solution structure using NMR spectroscopy. The structure consists of a solvent-accessible β-hairpin protruding from a disulphide-bonded globular core comprising four β-turns. The three intramolecular disulphide bonds form a cystine knot motif similar to that seen in several other neurotoxic peptides. Despite limited sequence identity, ω-ACTX-HV1 displays significant structural homology with the ω-agatoxins and ω-conotoxins, both of which are vertebrate calcium channel antagonists; however, in contrast with these toxins, we show that ω-ACTX-HV1 inhibits insect, but not mammalian, voltage-gated calcium channel currents.

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Authors and Affiliations

  1. Department of Biochemistry, University of Sydney, Sydney, New South Wales, 2006, Australia

    Jamie I. Fletcher & Glenn F. King

  2. Department of Pharmacology, University of Sydney, Sydney, New South Wales, 2006, Australia

    Mark Connor, Merlin E.H. Howden & Macdonald J. Christie

  3. Department of Biochemistry, University of Queensland, St. Lucia, QLD, 4067, Australia

    Ross Smith

  4. European Molecular Biology Laboratory, D-69012, Heidelberg, Germany

    Séan I. O'Donoghue & Michael Nilges

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Fletcher, J., Smith, R., O'Donoghue, S. et al. The structure of a novel insecticidal neurotoxin, ω-atracotoxin-HV1, from the venom of an Australian funnel web spider. Nat Struct Mol Biol 4, 559–566 (1997). https://doi.org/10.1038/nsb0797-559

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