View source for 1vtx


==DELTA-ATRACOTOXIN-HV1 (VERSUTOXIN) FROM HADRONYCHE VERSUTA, NMR, 20 STRUCTURES==
<StructureSection load='1vtx' size='340' side='right'caption='[[1vtx]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1vtx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Hadronyche_versuta Hadronyche versuta]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VTX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1VTX FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1vtx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vtx OCA], [https://pdbe.org/1vtx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1vtx RCSB], [https://www.ebi.ac.uk/pdbsum/1vtx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1vtx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/D1A_HADVE D1A_HADVE] Inhibits tetrodotoxin-sensitive voltage-gated sodium channels (Nav) by binding to site 3. Slows the inactivation, and causes a prolongation of action potential duration resulting in repetitive firing in autonomic and motor nerve fibers. Does not depolarize the resting potential. Does not affect tetrodotoxin-resistant sodium channels. This lethal neurotoxin is active on both insect and mammalian voltage-gated sodium channels. Pan-neuronal expression in Drosophila is lethal but flies engineered to express the toxin only in pacemaker neurons have profound defects in circadian rhythm but a normal lifespan.<ref>PMID:11171353</ref> <ref>PMID:11874465</ref> <ref>PMID:18986214</ref> <ref>PMID:7816562</ref> <ref>PMID:8281423</ref> <ref>PMID:9028001</ref> <ref>PMID:9845331</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vt/1vtx_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1vtx ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.

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<ref>PMID:9384567</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1vtx" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Hadronyche versuta]]
[[Category: Large Structures]]
[[Category: Chapman BE]]
[[Category: Fletcher JI]]
[[Category: King GF]]