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.
|Number of pages||8|
|Journal||Nature Structural Biology|
|Publication status||Published - 1997|