Hainantoxin-III(HNTX-III;hainantoxin-3) isapeptidethathasbeenisolatedfromthevenomoftheChinesebirdspider Seleconosmiahainana. Hainantoxin-III specifically blocksmammalianneuronaltetrodotoxin-sensitivevoltage-gatedsodiumchannels (VGSCs). HainantoxinIII wasfoundinactiveontetrodotoxin-resistantVGSCsandvoltage-gatedCa2+channels(bothhighandlowvoltage-activated).
Hainantoxin-III stronglydepressedtheamplitudeofratDRGtetrodotoxin-sensitiveNa+ currentswithanIC50 valueof1.1nM.Like Hainantoxin-IV, Hainantoxin-III causesahyperpolarizingshiftofabout10mVinthevoltagemidpointofsteady-stateNa+ channelinactivation.Similarto Huwentoxin-IV, Hainantoxin-III and Hainantoxin-IV donotaffecttheactivationandinactivationkineticsofNa+ currents.
Hainantoxin-IIIinhibitsNav1.7 currentamplitudewithoutsignificantlyalteringtheactivationandinactivationkinetics.Hainantoxin-III increasesthedeactivationoftheNav1.7currentafterextremedepolarizations. Hainantoxin-III seemstointeractwithsite4andtotrapthedomainIIvoltagesensorintheclosedstate.TheinhibitionofNav1.7byhainantoxin-IIIisreversIBLeuponwashing,butnoreversibilitywasobservedfor Hainantoxin-IV and Huwentoxin-IV. Hainantoxin-IIIwasshowntoblock Nav1.1,Nav1.2,Nav1.3andNav1.7 expressedinHEK293cellswithIC50 valuesof1.27µM,275nM,491nMand232nM,respectively.
Description:
AAsequence: Gly-Cys2-Lys-Gly-Phe-Gly-Asp-Ser-Cys9-Thr-Pro-Gly-Lys-Asn-Glu-Cys16-Cys17-Pro-Asn-Tyr-Ala-Cys22-Ser-Ser-Lys-His-Lys-Trp-Cys29-Lys-Val-Tyr-Leu-NH2
Disulfidebonds: Cys2-Cys17,Cys9-Cys22,andCys16-Cys29
Length(aa): 33
Formula: C154H228N44O45S6
MolecularWeight: 3608.20Da
Appearance:Whitelyophilizedsolid
Solubility: waterandsalinebuffer
CASnumber: Notavailable
Source: Synthetic
Purityrate: >97%
Reference:
Inhibitionofneuronaltetrodotoxin-sensitiveNa+channelsbytwospidertoxins:hainantoxin-IIIandhainantoxin-IV.
Hainantoxin-IIIandhainantoxin-IV,isolatedfromthevenomoftheChinesebirdspiderSeleconosmiahainana,areneurotoxicpeptidescomposedof33-35residueswiththreedisulfidebonds.Usingwhole-cellpatch-clamptechnique,weinvestigatedtheiractiononionicchannelsofadultratdorsalrootganglionneurons.ItwasfoundthatthetwotoxinsdidnotaffectCa2+channels(bothhighvoltageactivatedandlowvoltageactivatedtypes)nortetrodotoxin-resistantvoltage-gatedNa+channels(VGSCs).However,hainantoxin-IIIandhainantoxin-IVstronglydepressedtheamplitudeoftetrodotoxin-sensitiveNa+currentswithIC50valuesof1.1and44.6nM,respectively.Bothhainantoxin-III(1nM)andhainantoxin-IV(50nM)causedahyperpolarizingshiftofabout10mVinthevoltagemidpointofsteady-stateNa+channelinactivation,buttheyshoweddifferenceinthereprimekineticsofVGSCs:hainantoxin-IIIsignificantlydecreasedtherecoveryratefrominactivationataprepulsepotentialof-80mVwhilehainantoxin-IVdidnotdo.Itisinterestingtonotethatsimilartohuwentoxin-IV,thetwohainantoxinsdidnotaffecttheactivationandinactivationkineticsofNa+currentsandataconcentrationof1microMtheycompletelyinhibitedtheslowinginactivationcurrentsinducedbyBMK-I(toxinIfromthescorpionButhusmartensiKarsch),ascorpionalpha-liketoxin.Theresultsindicatethathainantoxin-IIIandhainantoxin-IVarenovelspidertoxinsandaffectthemammalneuralNa+channelsthroughamechanismquitedifferentfromotherspidertoxinstargetingtheneuralreceptorsite3,suchasdelta-aractoxinsandmu-agatoxins.
XiaoY, etal.(2003)Inhibitionofneuronaltetrodotoxin-sensitiveNa+channelsbytwospidertoxins:hainantoxin-IIIandhainantoxin-IV. EurJPharmacol. PMID: 14512091
StructureandFunctionofHainantoxin-III,aSelectiveAntagoNISTofNeuronalTetrodotoxin-sensitiveVoltage-gatedSodiumChannelsIsolatedfromtheChineseBirdSpiderOrnithoctonushainana
Inthepresentstudy,weinvestigatedthestructureandfunctionofhainantoxin-III(HNTX-III),a33-residuepolypeptidefromthevenomofthespiderOrnithoctonushainana.Itisaselectiveantagonistofneuronaltetrodotoxin-sensitivevoltage-gatedsodiumchannels.HNTX-IIIsuppressedNav1.7currentamplitudewithoutsignificantlyalteringtheactivation,inactivation,andreprimingkinetics.Shortextremedepolarizationspartiallyactivatedthetoxin-boundchannel,indicatingvoltage-dependentinhibitionofHNTX-III.HNTX-IIIincreasedthedeactivationoftheNav1.7currentafterextremedepolarizations.TheHNTX-III·Nav1.7complexwasgraduallydissociateduponprolongedstrongdepolarizationsinavoltage-dependentmanner,andtheunboundtoxinreboundtoNav1.7afteralongrepolarization.Moreover,analysisofchimericchannelsshowedthattheDIIS3-S4linkerwascriticalforHNTX-IIIbindingtoNav1.7.ThesedataareconsistentwithHNTX-IIIinteractingwithNav1.7site4andtrappingthedomainIIvoltagesensorintheclosedstate.ThesolutionstructureofHNTX-IIIwasdeterminedbytwo-dimensionalNMRandshowntopossessaninhibitorcystineknotmotif.Structuralanalysisindicatedthatcertainbasic,hydrophobic,andaromaticresiduesmainlylocalizedintheCterminusmayconstituteanamphiphilicsurfacepotentiallyinvolvedinHNTX-IIIbindingtoNav1.7.Takentogether,ourresultsshowthatHNTX-IIIisdistinctfromβ-scorpiontoxinsandotherβ-spidertoxinsinitsmechanismofactionandbindingspecificityandaffinity.Thepresentfindingscontributetoourunderstandingofthemechanismoftoxin-sodiumchannelinteractionandprovideausefultoolfortheinvestigationofthestructureandfunctionofsodiumchannelisoformsandforthedevelopmentofanalgesics.
LiuZ., etal. (2013)StructureandFunctionofHainantoxin-III,aSelectiveAntagonistofNeuronalTetrodotoxin-sensitiveVoltage-gatedSodiumChannelsIsolatedfromtheChineseBirdSpiderOrnithoctonushainana. JBC. PMID: 23703613
Determinationofdisulfidebridgesoftwospidertoxins:Hainantoxin-IIIandHainantoxin-IV
WangW,etal.(2009) Determinationofdisulfidebridgesoftwospidertoxins:Hainantoxin-IIIandHainantoxin-IV. J.Venom.Anim. Toxinsincl.Trop.Dis
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