The structure of versutoxin ($\delta$-atracotoxin-Hv1) provides insights into the binding of site 3 neurotoxins to the voltage-gated sodium channel

The structure of versutoxin ($\delta$-atracotoxin-Hv1) provides insights into the binding of site 3 neurotoxins to the voltage-gated sodium channel. Fletcher, J. I., Chapman, B. E., Mackay, J. P., Howden, M. E., & King, G. F. Structure, 5(11):1525–1535, nov, 1997.
$The structure of versutoxin ($\delta$-atracotoxin-Hv1) provides insights into the binding of site 3 neurotoxins to the voltage-gated sodium channel [link]$ Paper doi abstract bibtex

Background: Versutoxin ($\delta$-ACTX-Hv1) is the major component of the venom of the Australian Blue Mountains funnel web spider, Hadronyche versuta. $\delta$-ACTX-Hv1 produces potentially fatal neurotoxic symptoms in primates by slowing the inactivation of voltage-gated sodium channels; $\delta$-ACTX-Hv1 is therefore a useful tool for studying sodium channel function. We have determined the three-dimensional structure of $\delta$-ACTX-Hv1 as the first step towards understanding the molecular basis of its interaction with these channels. Results: The solution structure of $\delta$-ACTX-Hv1, determined using NMR spectroscopy, comprises a core $\beta$ region containing a triple-stranded antiparallel $\beta$ sheet, a thumb-like extension protruding from the $\beta$ region and a C-terminal 310 helix that is appended to the $\beta$ domain by virtue of a disulphide bond. The $\beta$ region contains a cystine knot motif similar to that seen in other neurotoxic polypeptides. The structure shows homology with $\mu$-agatoxin-I, a spider toxin that also modifies the inactivation kinetics of vertebrate voltage-gated sodium channels. More surprisingly, $\delta$-ACTX-Hv1 shows both sequence and structural homology with gurmarin, a plant polypeptide. This similarity leads us to suggest that the sweet-taste suppression elicited by gurmarin may result from an interaction with one of the downstream ion channels involved in sweet-taste transduction. Conclusions: $\delta$-ACTX-Hv1 shows no structural homology with either sea anemone or $\alpha$-scorpion toxins, both of which also modify the inactivation kinetics of voltage-gated sodium channels by interacting with channel recognition site 3. However, we have shown that $\delta$-ACTX-Hv1 contains charged residues that are topologically related to those implicated in the binding of sea anemone and $\alpha$-scorpion toxins to mammalian voltage-gated sodium channels, suggesting similarities in their mode of interaction with these channels.

@article{Fletcher1997,
abstract = {Background: Versutoxin ($\delta$-ACTX-Hv1) is the major component of the venom of the Australian Blue Mountains funnel web spider, Hadronyche versuta. $\delta$-ACTX-Hv1 produces potentially fatal neurotoxic symptoms in primates by slowing the inactivation of voltage-gated sodium channels; $\delta$-ACTX-Hv1 is therefore a useful tool for studying sodium channel function. We have determined the three-dimensional structure of $\delta$-ACTX-Hv1 as the first step towards understanding the molecular basis of its interaction with these channels. Results: The solution structure of $\delta$-ACTX-Hv1, determined using NMR spectroscopy, comprises a core $\beta$ region containing a triple-stranded antiparallel $\beta$ sheet, a thumb-like extension protruding from the $\beta$ region and a C-terminal 310 helix that is appended to the $\beta$ domain by virtue of a disulphide bond. The $\beta$ region contains a cystine knot motif similar to that seen in other neurotoxic polypeptides. The structure shows homology with $\mu$-agatoxin-I, a spider toxin that also modifies the inactivation kinetics of vertebrate voltage-gated sodium channels. More surprisingly, $\delta$-ACTX-Hv1 shows both sequence and structural homology with gurmarin, a plant polypeptide. This similarity leads us to suggest that the sweet-taste suppression elicited by gurmarin may result from an interaction with one of the downstream ion channels involved in sweet-taste transduction. Conclusions: $\delta$-ACTX-Hv1 shows no structural homology with either sea anemone or $\alpha$-scorpion toxins, both of which also modify the inactivation kinetics of voltage-gated sodium channels by interacting with channel recognition site 3. However, we have shown that $\delta$-ACTX-Hv1 contains charged residues that are topologically related to those implicated in the binding of sea anemone and $\alpha$-scorpion toxins to mammalian voltage-gated sodium channels, suggesting similarities in their mode of interaction with these channels.},
annote = {cited By 102},
author = {Fletcher, Jamie I. and Chapman, Bogdan E. and Mackay, Joel P. and Howden, Merlin E.H. and King, Glenn F.},
doi = {10.1016/S0969-2126(97)00301-8},
issn = {09692126},
journal = {Structure},
keywords = {Anthopleurin,Gurmarin,Sodium channel inactivation,Versutoxin,$\alpha$-scorpion toxin},
month = {nov},
number = {11},
pages = {1525--1535},
pmid = {9384567},
title = {{The structure of versutoxin ($\delta$-atracotoxin-Hv1) provides insights into the binding of site 3 neurotoxins to the voltage-gated sodium channel}},
url = {https://linkinghub.elsevier.com/retrieve/pii/S0969212697003018},
volume = {5},
year = {1997}
}

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Results: The solution structure of $\\delta$-ACTX-Hv1, determined using NMR spectroscopy, comprises a core $\\beta$ region containing a triple-stranded antiparallel $\\beta$ sheet, a thumb-like extension protruding from the $\\beta$ region and a C-terminal 310 helix that is appended to the $\\beta$ domain by virtue of a disulphide bond. The $\\beta$ region contains a cystine knot motif similar to that seen in other neurotoxic polypeptides. The structure shows homology with $\\mu$-agatoxin-I, a spider toxin that also modifies the inactivation kinetics of vertebrate voltage-gated sodium channels. More surprisingly, $\\delta$-ACTX-Hv1 shows both sequence and structural homology with gurmarin, a plant polypeptide. This similarity leads us to suggest that the sweet-taste suppression elicited by gurmarin may result from an interaction with one of the downstream ion channels involved in sweet-taste transduction. 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This similarity leads us to suggest that the sweet-taste suppression elicited by gurmarin may result from an interaction with one of the downstream ion channels involved in sweet-taste transduction. Conclusions: $\\delta$-ACTX-Hv1 shows no structural homology with either sea anemone or $\\alpha$-scorpion toxins, both of which also modify the inactivation kinetics of voltage-gated sodium channels by interacting with channel recognition site 3. 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