GsAF-1(alsotermedβ-theraphotoxin-Gr1b,GsAF-I)wasoriginallyisolatedfromthevenomofGrammostolaroseaspider.GsAF-Ipeptidetoxinisreportedtoblockthefollowingvoltage-gatedsodiumchannelisoforms:Nav1.1,Nav1.2,Nav1.3,Nav1.4,Nav1.6andNav1.7withrespectiveIC50valuesof 0.4,0.6,1.3,0.3,1.2and0.04µM.Inaddition,thetoxinblocksthehERG1isoformwithanIC50valueof4.8µM.
Description:
AAsequence:Tyr-Cys2-Gln-Lys-Trp-Leu-Trp-Thr-Cys9-Asp-Ser-Glu-Arg-Lys-Cys15-Cys16-Glu-Asp-Met-Val-Cys21-Arg-Leu-Trp-Cys25-Lys-Lys-Arg-Leu-NH2
Disulfidebonds:Cys2-Cys16,Cys9-Cys21,andCys15-Cys25
Length(aa):29
Formula:C160H245N47O41S7
MolecularWeight: 3707.48Da
Appearance:Whitelyophilizedsolid
Solubility:aqueousbuffer
CASnumber:notavailable
Source:Synthetic
Purityrate:>98%
Reference:
TargetPromiscuityandHeterogeneousEffectsofTarantulaVenomPeptidesAffectingNa+andK+IonChannels
Venom-derivedpeptidemodulatorsofionchannelgatingareregardedasessentialtoolsforunderstandingthemolecularmotionsthatoccurduringtheopeningandclosingofionchannels.Inthisstudy,wepresentthecharacterizationoffivespidertoxinson12humanvoltage-gatedionchannels,followingobservationsaboutthetargetpromiscuityofsomespidertoxinsandtheongoingrevisionoftheir“canonical”gating-modifyingmodeofaction.Thepeptideswerepurified denovo fromthevenomof Grammostolarosea tarantulas,andtheirsequenceswereconfirmedbyEdmandegradationandmassspectrometryanalysis.Theireffectsonseventetrodotoxin-sensitiveNa+ channels,thethreehuman ether-à-go-go (hERG)-relatedK+ channels,andtwohuman Shaker-relatedK+ channelswereextensivelycharacterizedbyelectrophysiologicaltechniques.AllthepeptidesinhibitedionconductionthroughalltheNa+channelstested,althoughwithdistinctivepatterns.ThepeptidesalsoaffectedthethreepharmaceuticallyrelevanthERGisoformsdifferently.Athigherconcentrations,allpeptidesalsomodifiedthegatingoftheNa+ channelsbyshiftingtheactivationtomorepositivepotentials,whereasmorecomplexeffectswererecordedonhERGchannels.Noeffectswereevidentonthetwo Shaker-relatedK+ channelsatconcentrationswellabovetheIC50 valuefortheaffectedchannels.Giventhesequencediversityofthetestedpeptides,weproposethattarantulatoxinsshouldbeconsideredbothasmultimodeandtarget-promiscuousionchannelmodulators;bothfeaturesshouldnotbeignoredwhenextractingmechaNISTicinterpretationsaboutionchannelgating.Ourobservationscouldalsoaidinfuturestructure-functionstudiesandmighthelpthedevelopmentofnovelionchannel-specificdrugs.
ELISARedaelli,etal.(2010)TargetPromiscuityandHeterogeneousEffectsofTarantulaVenomPeptidesAffectingNa+andK+IonChannels.JBC.PMID:19955179
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