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1vtx

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(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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Revision as of 03:00, 21 November 2007


1vtx

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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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