This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

1vtx

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 09:44, 29 September 2021

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.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[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

↑ 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, 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
↑ 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
↑ 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
↑ 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"

@@ Line 3: / Line 3: @@
 <StructureSection load='1vtx' size='340' side='right'caption='[[1vtx]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1vtx]] is a 1 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1VTX FirstGlance]. <br>
+<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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1vtx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vtx OCA], [http://pdbe.org/1vtx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1vtx RCSB], [http://www.ebi.ac.uk/pdbsum/1vtx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1vtx ProSAT]</span></td></tr>
+</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 ==
-[[http://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/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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

1vtx

From Proteopedia

Revision as of 09:44, 29 September 2021

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?)

Views

Personal tools

Navigation

Search

Toolbox