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

Jamie I. Fletcher, Ross Smith, Séan I. O'Donoghue, Michael Nilges, Mark Connor, Merlin E H Howden, Macdonald J. Christie, Glenn F. King*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

154 Citations (Scopus)

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-HV1inhibits insect, but not mammalian, voltage-gated calcium channel currents.

Original languageEnglish
Pages (from-to)559-566
Number of pages8
JournalNature Structural Biology
Volume4
Issue number7
DOIs
Publication statusPublished - 1997
Externally publishedYes

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