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

The structure of versutoxin (δ-atracotoxin-Hv1) provides insights into the binding of site 3 neurotoxins to the voltage-gated sodium channel. Fletcher, J., Chapman, B., Mackay, J., Howden, M., & King, G. Structure, 5(11):1525-1535, 1997.
doi abstract bibtex

Background: Versutoxin (δ-ACTX-Hv1) is the major component of the venom of the Australian Blue Mountains funnel web spider, Hadronyche versuta. δ-ACTX-Hv1 produces potentially fatal neurotoxic symptoms in primates by slowing the inactivation of voltage-gated sodium channels; δ-ACTX-Hv1 is therefore a useful tool for studying sodium channel function. We have determined the three-dimensional structure of δ-ACTX-Hv1 as the first step towards understanding the molecular basis of its interaction with these channels. Results: The solution structure of δ-ACTX-Hv1, determined using NMR spectroscopy, comprises a core β region containing a triple-stranded antiparallel β sheet, a thumb-like extension protruding from the β region and a C-terminal 310 helix that is appended to the β domain by virtue of a disulphide bond. The β region contains a cystine knot motif similar to that seen in other neurotoxic polypeptides. The structure shows homology with μ-agatoxin-I, a spider toxin that also modifies the inactivation kinetics of vertebrate voltage-gated sodium channels. More surprisingly, δ-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: δ-ACTX-Hv1 shows no structural homology with either sea anemone or α-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 δ-ACTX-Hv1 contains charged residues that are topologically related to those implicated in the binding of sea anemone and α-scorpion toxins to mammalian voltage-gated sodium channels, suggesting similarities in their mode of interaction with these channels.

@article{
 title = {The structure of versutoxin (δ-atracotoxin-Hv1) provides insights into the binding of site 3 neurotoxins to the voltage-gated sodium channel},
 type = {article},
 year = {1997},
 pages = {1525-1535},
 volume = {5},
 id = {c641551b-c512-3935-9b0e-32d0d876b55e},
 created = {2023-01-10T01:46:53.511Z},
 file_attached = {false},
 profile_id = {a5a2ab6f-a8b5-3db6-97bc-618752ee4386},
 group_id = {bc1ab1d4-9e57-37e6-9fb5-435fca0ee9d2},
 last_modified = {2023-01-10T01:46:53.511Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Versutoxin (δ-ACTX-Hv1) is the major component of the venom of the Australian Blue Mountains funnel web spider, Hadronyche versuta. δ-ACTX-Hv1 produces potentially fatal neurotoxic symptoms in primates by slowing the inactivation of voltage-gated sodium channels; δ-ACTX-Hv1 is therefore a useful tool for studying sodium channel function. We have determined the three-dimensional structure of δ-ACTX-Hv1 as the first step towards understanding the molecular basis of its interaction with these channels. Results: The solution structure of δ-ACTX-Hv1, determined using NMR spectroscopy, comprises a core β region containing a triple-stranded antiparallel β sheet, a thumb-like extension protruding from the β region and a C-terminal 310 helix that is appended to the β domain by virtue of a disulphide bond. The β region contains a cystine knot motif similar to that seen in other neurotoxic polypeptides. The structure shows homology with μ-agatoxin-I, a spider toxin that also modifies the inactivation kinetics of vertebrate voltage-gated sodium channels. More surprisingly, δ-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: δ-ACTX-Hv1 shows no structural homology with either sea anemone or α-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 δ-ACTX-Hv1 contains charged residues that are topologically related to those implicated in the binding of sea anemone and α-scorpion toxins to mammalian voltage-gated sodium channels, suggesting similarities in their mode of interaction with these channels.},
 bibtype = {article},
 author = {Fletcher, J.I. and Chapman, B.E. and Mackay, J.P. and Howden, M.E.H. and King, G.F.},
 doi = {10.1016/S0969-2126(97)00301-8},
 journal = {Structure},
 number = {11}
}

Downloads: 0

{"_id":"xstdoNXuvHwrXw4xv","bibbaseid":"fletcher-chapman-mackay-howden-king-thestructureofversutoxinatracotoxinhv1providesinsightsintothebindingofsite3neurotoxinstothevoltagegatedsodiumchannel-1997","author_short":["Fletcher, J.","Chapman, B.","Mackay, J.","Howden, M.","King, G."],"bibdata":{"title":"The structure of versutoxin (δ-atracotoxin-Hv1) provides insights into the binding of site 3 neurotoxins to the voltage-gated sodium channel","type":"article","year":"1997","pages":"1525-1535","volume":"5","id":"c641551b-c512-3935-9b0e-32d0d876b55e","created":"2023-01-10T01:46:53.511Z","file_attached":false,"profile_id":"a5a2ab6f-a8b5-3db6-97bc-618752ee4386","group_id":"bc1ab1d4-9e57-37e6-9fb5-435fca0ee9d2","last_modified":"2023-01-10T01:46:53.511Z","read":false,"starred":false,"authored":false,"confirmed":false,"hidden":false,"private_publication":false,"abstract":"Background: Versutoxin (δ-ACTX-Hv1) is the major component of the venom of the Australian Blue Mountains funnel web spider, Hadronyche versuta. δ-ACTX-Hv1 produces potentially fatal neurotoxic symptoms in primates by slowing the inactivation of voltage-gated sodium channels; δ-ACTX-Hv1 is therefore a useful tool for studying sodium channel function. We have determined the three-dimensional structure of δ-ACTX-Hv1 as the first step towards understanding the molecular basis of its interaction with these channels. Results: The solution structure of δ-ACTX-Hv1, determined using NMR spectroscopy, comprises a core β region containing a triple-stranded antiparallel β sheet, a thumb-like extension protruding from the β region and a C-terminal 310 helix that is appended to the β domain by virtue of a disulphide bond. The β region contains a cystine knot motif similar to that seen in other neurotoxic polypeptides. The structure shows homology with μ-agatoxin-I, a spider toxin that also modifies the inactivation kinetics of vertebrate voltage-gated sodium channels. More surprisingly, δ-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: δ-ACTX-Hv1 shows no structural homology with either sea anemone or α-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 δ-ACTX-Hv1 contains charged residues that are topologically related to those implicated in the binding of sea anemone and α-scorpion toxins to mammalian voltage-gated sodium channels, suggesting similarities in their mode of interaction with these channels.","bibtype":"article","author":"Fletcher, J.I. and Chapman, B.E. and Mackay, J.P. and Howden, M.E.H. and King, G.F.","doi":"10.1016/S0969-2126(97)00301-8","journal":"Structure","number":"11","bibtex":"@article{\n title = {The structure of versutoxin (δ-atracotoxin-Hv1) provides insights into the binding of site 3 neurotoxins to the voltage-gated sodium channel},\n type = {article},\n year = {1997},\n pages = {1525-1535},\n volume = {5},\n id = {c641551b-c512-3935-9b0e-32d0d876b55e},\n created = {2023-01-10T01:46:53.511Z},\n file_attached = {false},\n profile_id = {a5a2ab6f-a8b5-3db6-97bc-618752ee4386},\n group_id = {bc1ab1d4-9e57-37e6-9fb5-435fca0ee9d2},\n last_modified = {2023-01-10T01:46:53.511Z},\n read = {false},\n starred = {false},\n authored = {false},\n confirmed = {false},\n hidden = {false},\n private_publication = {false},\n abstract = {Background: Versutoxin (δ-ACTX-Hv1) is the major component of the venom of the Australian Blue Mountains funnel web spider, Hadronyche versuta. δ-ACTX-Hv1 produces potentially fatal neurotoxic symptoms in primates by slowing the inactivation of voltage-gated sodium channels; δ-ACTX-Hv1 is therefore a useful tool for studying sodium channel function. We have determined the three-dimensional structure of δ-ACTX-Hv1 as the first step towards understanding the molecular basis of its interaction with these channels. Results: The solution structure of δ-ACTX-Hv1, determined using NMR spectroscopy, comprises a core β region containing a triple-stranded antiparallel β sheet, a thumb-like extension protruding from the β region and a C-terminal 310 helix that is appended to the β domain by virtue of a disulphide bond. The β region contains a cystine knot motif similar to that seen in other neurotoxic polypeptides. The structure shows homology with μ-agatoxin-I, a spider toxin that also modifies the inactivation kinetics of vertebrate voltage-gated sodium channels. More surprisingly, δ-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: δ-ACTX-Hv1 shows no structural homology with either sea anemone or α-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 δ-ACTX-Hv1 contains charged residues that are topologically related to those implicated in the binding of sea anemone and α-scorpion toxins to mammalian voltage-gated sodium channels, suggesting similarities in their mode of interaction with these channels.},\n bibtype = {article},\n author = {Fletcher, J.I. and Chapman, B.E. and Mackay, J.P. and Howden, M.E.H. and King, G.F.},\n doi = {10.1016/S0969-2126(97)00301-8},\n journal = {Structure},\n number = {11}\n}","author_short":["Fletcher, J.","Chapman, B.","Mackay, J.","Howden, M.","King, G."],"biburl":"https://bibbase.org/service/mendeley/a5a2ab6f-a8b5-3db6-97bc-618752ee4386","bibbaseid":"fletcher-chapman-mackay-howden-king-thestructureofversutoxinatracotoxinhv1providesinsightsintothebindingofsite3neurotoxinstothevoltagegatedsodiumchannel-1997","role":"author","urls":{},"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://bibbase.org/service/mendeley/a5a2ab6f-a8b5-3db6-97bc-618752ee4386","dataSources":["ya2CyA73rpZseyrZ8","4BKYoCQJ3ndMcbbtH","2252seNhipfTmjEBQ"],"keywords":[],"search_terms":["structure","versutoxin","atracotoxin","hv1","provides","insights","binding","site","neurotoxins","voltage","gated","sodium","channel","fletcher","chapman","mackay","howden","king"],"title":"The structure of versutoxin (δ-atracotoxin-Hv1) provides insights into the binding of site 3 neurotoxins to the voltage-gated sodium channel","year":1997}