α-conotoxinMI (alpha-conotoxinMI)isaconotoxinthathasbeenisolatedfromthevenomoftheconesnailConusmagus. α-conotoxinMIisacompetitiveantagoNISTofthemuscle-typenicotinicacetylcholinereceptors(nAChR)suchas α-conotoxinGIord-Turbocurarine.ItbindstothereceptorwithaKdvalue~0,94nM. α-conotoxinMIallowstodistinguishbetweenthetwoagonistsitesasitbinds10,000-foldmoretightlytotheα/δthantotheα/γsite.
Description:
AAsequence: Gly-Arg-Cys3-Cys4-His-Pro-Ala-Cys8-Gly-Lys-Asn-Tyr-Ser-Cys14-NH2
Disulfidebonds: Cys3-Cys8 andCys4-Cys14
Length(aa): 14
Formula: C58H88N22O17S4
MolecularWeight: 1495.08Da
Appearance:Whitelyophilizedsolid
Solubility: waterorsalinebuffer
CASnumber: [83481-45-2]Source: Synthetic
Purityrate: >97%
Reference:
Criticalresiduesinfluencetheaffinityandselectivityofalpha-conotoxinMIfornicotinicacetylcholinereceptors
Themammalianskeletalmuscleacetylcholinereceptorcontainstwononequivalentacetylcholinebindingsites,oneeachatthealpha/deltaandalpha/gammasubunitinterfaces.Alpha-ConotoxinMI,a14-aminoacidcompetitiveantagonist,bindsatbothinterfacesbuthasapproximately10(4)higheraffinityforthealpha/deltasite.Weperformedan“alaninewalk”toidentifytheresiduesinalpha-MIthatcontributetothisselectiveinteractionwiththealpha/deltasite.ElectrophysiologicalmeasurementswithXenopusoocytesexpressingnormalreceptorsorreceptorslackingeitherthegammaordeltasubunitweremadetoassaytoxin-receptorinteraction.Alaninesubstitutionsinmostaminoacidpositionshadonlymodesteffectsontoxinpotencyateitherbindingsite.However,substitutionsintwopositions,proline-6andtyrosine-12,dramaticallyreducedtoxinpotencyatthehigh-affinityalpha/deltasitewhilehavingcomparativelylittleeffectonlow-affinityalpha/gammabinding.Whentyrosine-12wasreplacedbyalanine,thetoxin’sselectivityforthehigh-affinitysite(relativetothatforthelow-affinitysite)wasreducedfrom45,000-to30-fold.Aseriesofadditionalaminoacidsubstitutionsinthispositionshowedthatincreasingsidechainsize/hydrophobicityincreasestoxinpotencyatthealpha/deltasitewithoutaffectingalpha/gammabinding.Incontrast,whentyrosine-12isdiiodinated,toxinbindingisnearlyirreversIBLeatthealpha/deltasitebutalsoincreasesbyapproximately500-foldatthealpha/gammasite.Theeffectsofposition12substitutionsareaccountedforalmostentirelybychangesintherateoftoxindissociationfromthehigh-affinityalpha/deltabindingsite.
Jacobsen,R.B., etal.(1999) Criticalresiduesinfluencetheaffinityandselectivityofalpha-conotoxinMIfornicotinicacetylcholinereceptors, Biochemistry. PMID:10529206
ConotoxinMI.Disulfidebondingandconformationalstates
Gray,W.R., etal.(1983) ConotoxinMI.Disulfidebondingandconformationalstates, JBiolChem. PMID:6630187
Site-specificchargeinteractionsofalpha-conotoxinMIwiththenicotinicacetylcholinereceptor
PapineniRV., etal. (2001) Site-specificchargeinteractionsofalpha-conotoxinMIwiththenicotinicacetylcholinereceptor. JBiolChem. PMID:11323431 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。
