α-conotoxinPeIAisaconotoxinthathasbeenisolatedfromthevenomof Conuspergrandis. α-conotoxinPeIA discriminatesbetweenα9α10andα7nicotinicacetylcholinereceptors(AChRs)withIC50 valuesof7-50nM(dependingoftheauthors)and1.8µM,respectively.Thetoxinisalsoknowntoblockα3β2nicotinicAChRs(withanIC50 of97nM)andblockvoltage-gatedN-typeCa2+ channelsinratDRGneuronswithanIC50 of1.1nM.NosignificantinhibitionofACh-evokedcurrentsfornicotinicα4β2andmuscleαβγδAChRsby1µM α-conotoxinPeIA wasobserved.Theactionof α-conotoxinPeIA isfullyreversIBLeafterwashoutofthepeptideintheextracellularmedium.
Description:
AAsequence: Gly-Cys2-Cys3-Ser-His-Pro-Ala-Cys8-Ser-Val-Asn-His-Pro-Glu-Leu-Cys16-NH2
Disulfidebonds: Cys2-Cys8,Cys3-Cys16
Length(aa): 16
Formula: C65H98N22O21S4
MolecularWeight: 1651.9Da
Appearance: Whitelyophilizedsolid
Solubility: waterorsalinebuffer
CASnumber: notavailable
Source: Synthetic
Purityrate: >99%
Reference:
StructureandActivityofα-ConotoxinPeIAatNicotinicAcetylcholineReceptorSubtypesandGABABReceptor-coupledN-typeCalciumChannels
α-Conotoxinsarepeptidesfromconesnailsthattargetthenicotinicacetylcholinereceptor(nAChR).RgIAandVc1.1haveanalgesicactivityinanimalpainmodels.Bothpeptidestargettheα9α10nAChRandinhibitN-typecalciumchannelsviaGABA(B)receptoractivation,butthemechanismofactionofanalgesicactivityisunknown.PeIAhaspreviouslybeenshowntoinhibittheα9α10andα3β2nAChRs.Inthisstudy,wehavedeterminedthestructureofPeIAandshownthatitisalsoapotentinhibitorofN-typecalciumchannelsviaGABA(B)receptoractivation.Thecharacteristicα-conotoxinfoldispresentinPeIA,butithasadifferentdistributionofsurface-exposedhydrophobicandchargedresiduescomparedwithVc1.1.Thus,thesurfaceresiduedistribution,ratherthantheoverallfold,appearstoberesponsibleforthe50-foldincreaseinselectivityattheα3β2nAChRbyPeIArelativetoVc1.1.IncontrasttotheirdifferenceinpotencyatthenAChR,theequipotentactivityofPeIAandVc1.1attheGABA(B)receptorsuggeststhattheGABA(B)receptorismoretoleranttochangesinsurfaceresiduesthanisthenAChR.TheconservedAsp-Pro-ArgmotifofVc1.1andRgIA,whichiscrucialforpotencyattheα9α10nAChR,isnotrequiredforactivityatGABA(B)receptor/N-typecalciumchannelsbecausePeIAhasaHis-Pro-Alamotifintheequivalentposition.Thisstudyshowsthatdifferentstructure-activityrelationshipsareassociatedwiththetargetingoftheGABA(B)receptorversusnAChRs.FurThermore,thereisprobablyamuchmorediverserangeofconotoxinsthattargettheGABA(B)receptorthancurrentlyrealized.
DayN., etal. (2011)StructureandActivityofα-ConotoxinPeIAatNicotinicAcetylcholineReceptorSubtypesandGABABReceptor-coupledN-typeCalciumChannels. JBC. PMID: 21252227
Anovelα-conotoxin,PeIA,clonedfromConusPergrandis,discriminatesbetweenratα9α10andα7nicotiniccholinergicreceptor
McIntoshM., etal. (2005)Anovel α-conotoxin,PeIA,clonedfromConusPergrandis,discriminatesbetweenrat α9α10and α7nicotiniccholinergicreceptor. JBC. PMID: 15983035 Smartox生物素ProTx-I电压门控钠通道和T型Cav的阻断剂毒素I（ProTx-1；β-theraphotoxin-Tp1a） 是一种毒素，最初是从Prixopelma pruriens（秘鲁绿色天鹅绒狼蛛）的毒液中分离出来的。此毒素可逆地抑制抗河豚毒素（TTX）的通道 Na v 1.8（IC 50 = 27 nM）和 Na v 1.2，Na v 1.5和Na v 1.7 ，IC 50 值为50至100 nM。此外， ProTx-I 改变了T型Ca v 3.1通道的电压依赖性活动 （IC 50 = 50 nM），而不会影响灭活的电压依赖性。生物素ProTx-I是ProTx-I的生物素标签版本。
