1vtx
From Proteopedia
(New page: 200px<br /><applet load="1vtx" size="450" color="white" frame="true" align="right" spinBox="true" caption="1vtx" /> '''DELTA-ATRACOTOXIN-HV1 (VERSUTOXIN) FROM HADR...) |
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| - | [[Image:1vtx.jpg|left|200px]]<br /><applet load="1vtx" size=" | + | [[Image:1vtx.jpg|left|200px]]<br /><applet load="1vtx" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1vtx" /> | caption="1vtx" /> | ||
'''DELTA-ATRACOTOXIN-HV1 (VERSUTOXIN) FROM HADRONYCHE VERSUTA, NMR, 20 STRUCTURES'''<br /> | '''DELTA-ATRACOTOXIN-HV1 (VERSUTOXIN) FROM HADRONYCHE VERSUTA, NMR, 20 STRUCTURES'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: Versutoxin (delta-ACTX-Hv1) is the major component of the | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1VTX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Hadronyche_versuta Hadronyche versuta]. Full crystallographic information is available from [http:// | + | 1VTX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Hadronyche_versuta Hadronyche versuta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VTX OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Hadronyche versuta]] | [[Category: Hadronyche versuta]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Chapman, B | + | [[Category: Chapman, B E.]] |
| - | [[Category: Fletcher, J | + | [[Category: Fletcher, J I.]] |
| - | [[Category: King, G | + | [[Category: King, G F.]] |
[[Category: cysteine knot]] | [[Category: cysteine knot]] | ||
[[Category: neurotoxin]] | [[Category: neurotoxin]] | ||
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[[Category: venom]] | [[Category: venom]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:38:24 2008'' |
Revision as of 13:38, 21 February 2008
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DELTA-ATRACOTOXIN-HV1 (VERSUTOXIN) FROM HADRONYCHE VERSUTA, NMR, 20 STRUCTURES
Overview
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.
About this Structure
1VTX is a Single protein structure of sequence from Hadronyche versuta. Full crystallographic information is available from OCA.
Reference
The structure of versutoxin (delta-atracotoxin-Hv1) provides insights into the binding of site 3 neurotoxins to the voltage-gated sodium channel., Fletcher JI, Chapman BE, Mackay JP, Howden ME, King GF, Structure. 1997 Nov 15;5(11):1525-35. PMID:9384567
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