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1vtx

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DELTA-ATRACOTOXIN-HV1 (VERSUTOXIN) FROM HADRONYCHE VERSUTA, NMR, 20 STRUCTURES

Structural highlights

1vtx is a 1 chain structure with sequence from Hadronyche versuta. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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^[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Grolleau F, Stankiewicz M, Birinyi-Strachan L, Wang XH, Nicholson GM, Pelhate M, Lapied B. Electrophysiological analysis of the neurotoxic action of a funnel-web spider toxin, delta-atracotoxin-HV1a, on insect voltage-gated Na+ channels. J Exp Biol. 2001 Feb;204(Pt 4):711-21. PMID:11171353
↑ Gilles N, Harrison G, Karbat I, Gurevitz M, Nicholson GM, Gordon D. Variations in receptor site-3 on rat brain and insect sodium channels highlighted by binding of a funnel-web spider delta-atracotoxin. Eur J Biochem. 2002 Mar;269(5):1500-10. PMID:11874465
↑ Wu Y, Cao G, Pavlicek B, Luo X, Nitabach MN. Phase coupling of a circadian neuropeptide with rest/activity rhythms detected using a membrane-tethered spider toxin. PLoS Biol. 2008 Nov 4;6(11):e273. doi: 10.1371/journal.pbio.0060273. PMID:18986214 doi:http://dx.doi.org/10.1371/journal.pbio.0060273
↑ Nicholson GM, Willow M, Howden ME, Narahashi T. Modification of sodium channel gating and kinetics by versutoxin from the Australian funnel-web spider Hadronyche versuta. Pflugers Arch. 1994 Oct;428(3-4):400-9. PMID:7816562
↑ Chieng B, Howden ME, Christie MJ. Australian funnel-web spider toxin, versutoxin, enhances spontaneous synaptic activity in single brain neurons in vitro. Brain Res. 1993 Oct 29;626(1-2):136-42. PMID:8281423
↑ Nicholson GM, Little MJ, Tyler M, Narahashi T. Selective alteration of sodium channel gating by Australian funnel-web spider toxins. Toxicon. 1996 Nov-Dec;34(11-12):1443-53. PMID:9028001
↑ Little MJ, Wilson H, Zappia C, Cestele S, Tyler MI, Martin-Eauclaire MF, Gordon D, Nicholson GM. Delta-atracotoxins from Australian funnel-web spiders compete with scorpion alpha-toxin binding on both rat brain and insect sodium channels. FEBS Lett. 1998 Nov 20;439(3):246-52. PMID:9845331
↑ Fletcher JI, Chapman BE, Mackay JP, Howden ME, King GF. The structure of versutoxin (delta-atracotoxin-Hv1) provides insights into the binding of site 3 neurotoxins to the voltage-gated sodium channel. Structure. 1997 Nov 15;5(11):1525-35. PMID:9384567

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1vtx"

Categories: Hadronyche versuta | Large Structures | Chapman BE | Fletcher JI | King GF

@@ Line 1: / Line 1: @@
 ==DELTA-ATRACOTOXIN-HV1 (VERSUTOXIN) FROM HADRONYCHE VERSUTA, NMR, 20 STRUCTURES==
-<StructureSection load='1vtx' size='340' side='right'caption='[[1vtx]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<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='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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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/TXDT1_HADVE TXDT1_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:8281423</ref> <ref>PMID:7816562</ref> <ref>PMID:9028001</ref> <ref>PMID:9845331</ref> <ref>PMID:11171353</ref> <ref>PMID:11874465</ref> <ref>PMID:18986214</ref>
+[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]]
@@ Line 33: / Line 34: @@
 [[Category: Hadronyche versuta]]
 [[Category: Large Structures]]
-[[Category: Chapman, B E]]
+[[Category: Chapman BE]]
-[[Category: Fletcher, J I]]
+[[Category: Fletcher JI]]
-[[Category: King, G F]]
+[[Category: King GF]]
-[[Category: Cysteine knot]]
-[[Category: Neurotoxin]]
-[[Category: Sodium channel toxin]]
-[[Category: Venom]]

1vtx

From Proteopedia

Current revision

DELTA-ATRACOTOXIN-HV1 (VERSUTOXIN) FROM HADRONYCHE VERSUTA, NMR, 20 STRUCTURES

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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