AuIB (P00095) Protein Card

General Information
Name AuIB
Alternative name(s) Au1b,gAuIB
Organism Conus aulicus
Organism region Indo-Pacific
Organism diet molluscivorous
Protein Type Wild type
Protein precursor AuIB precursor (2879)
Notes Inhibition of N-type Ca2+ channel current through the GABAB in rat DRG neurons with an IC50 of 1.5 nM (Klimis et al.). The specific receptor remains unclear.

Classification
Conopeptide class conotoxin
Gene superfamily A superfamily
Cysteine framework I
Pharmacological family alpha conotoxin

Sequence
GCCSYPPCFATNPDC(nh2)
Modified residues
positionsymbolname
16nh2C-term amidation
Sequence evidence protein level
Average Mass 1572.75
Monoisotopic Mass 1571.53
Isoelectric Point 5.47
Extinction Coefficient [280nm] 1490.00

Activity

IC50: Nicotinic acetylcholine receptors

TargetOrganismIC50nhillAgonistRef
α1β1γδM. musculus>75uM1uM AchLuo,S. et al. (1998)
α2β2R. norvegicus>75uM300uM AchLuo,S. et al. (1998)
α2β4R. norvegicus>75uM300uM AchLuo,S. et al. (1998)
α3β2R. norvegicus>75uM300uM AchLuo,S. et al. (1998)
α3β4R. norvegicus(a3b4 ratio 10:1)2.36uM1.68500uM AchGrishin,A.A. et al. (2010)
(a3b4 ratio 10:1)1.1uM1.3850uM AchGrishin,A.A. et al. (2010)
750nM1.05300uM AchLuo,S. et al. (1998)
9.1uM100nM epibatidineArmishaw,C.J. et al. (2011)
(a3b4 ratio 1:10)3.0uM150uM AchGrishin,A.A. et al. (2010)
966 nM1.1100 μM AChNicke,A. et al. (2003)
2.5uM+/-0.61.550-100uM AchLovelace,E.S. et al. (2011)
(a3b4 ratio 10:1)860nM1.37175uM AchGrishin,A.A. et al. (2010)
(a3b4 ratio 1:10)5.8uM1.635mM AchGrishin,A.A. et al. (2010)
(a3b4 ratio 1:10)1.24uM0.855uM AchGrishin,A.A. et al. (2010)
α4β2R. norvegicus>75uM300uM AchLuo,S. et al. (1998)
>300uM100nM epibatidineArmishaw,C.J. et al. (2011)
α4β4R. norvegicus>75uM300uM AchLuo,S. et al. (1998)
α7R. norvegicus>300uM100nM epibatidineArmishaw,C.J. et al. (2011)
~7.5uM1mM AchLuo,S. et al. (1998)
α9α10Unknown>1uM30uM AchKlimis,H. et al. (2011)

Percentage inhibition: Nicotinic acetylcholine receptors

TargetOrganism% inhibitionConcentrationAgonistRef
α3β4R. norvegicus(Adapted from reported "relative current amplitude". Error recorded as S.E. not S.D. )85+/-710 uM2.5 mM AChGrishin,A.A. et al. (2013)
([Q198A]α3 mutant receptor. Adapted from reported "relative current amplitude". Error recorded as S.)75+/-210 uM50 uM AChGrishin,A.A. et al. (2013)
(Adapted from reported "relative current amplitude". Error recorded as S.E. not S.D. )49+/-73 uM50 uM AChGrishin,A.A. et al. (2013)
9510uM50-100uM AchLovelace,E.S. et al. (2011)
([W59A]β4 mutant receptor. Adapted from reported "relative current amplitude". Error recorded as S.E)11+/-510 uM2.5 mM AChGrishin,A.A. et al. (2013)
00100nM epibatidineArmishaw,C.J. et al. (2011)
([W59A/K61A]β4 mutant receptor. Adapted from reported "relative current amplitude". Error= S.E.)11+/-810 uM2.5 mM AChGrishin,A.A. et al. (2013)
([K61A]β4 mutant receptor. Adapted from reported "relative current amplitude". Error recorded as S.E)34+/-310 uM2.5 mM AChGrishin,A.A. et al. (2013)
(Adapted from reported "relative current amplitude". Error recorded as S.E. not S.D. )83+/-210 uM50 uM AChGrishin,A.A. et al. (2013)
50Ach (3 uM)Wu et al. (2018)
95Ach (100 uM)Wu et al. (2018)
α4β2R. norvegicus00100nM epibatidineArmishaw,C.J. et al. (2011)
α7R. norvegicus00100nM epibatidineArmishaw,C.J. et al. (2011)
α9α10Unknown03uM30uM AchKlimis,H. et al. (2011)

Synthetic variants
Ac-AuIB(Ac)GCCSYPPCFATNPDC(nh2)
AuIB [ribbon]GCCSYPPCFATNPDC(nh2)
AuIB[C2H,C8F]GHCSYPPFFATNPDC(nh2)
AuIB[D14A]GCCSYPPCFATNPAC(nh2)
AuIB[F9(Nal)]GCCSYPPC(Nal)ATNPDC(nh2)
AuIB[F9A]GCCSYPPCAATNPDC(nh2)
AuIB[F9G]GCCSYPPCGATNPDC(nh2)
AuIB[F9W]GCCSYPPCWATNPDC(nh2)
AuIB[F9Y]GCCSYPPCYATNPDC(nh2)
AuIB[G1A]ACCSYPPCFATNPDC(nh2)
AuIB[N12A]GCCSYPPCFATAPDC(nh2)
AuIB[N12H]GCCSYPPCFATHPDC(nh2)
AuIB[P13A]GCCSYPPCFATNADC(nh2)
AuIB[P6A]GCCSYAPCFATNPDC(nh2)
AuIB[P7A]GCCSYPACFATNPDC(nh2)
AuIB[S4A]GCCAYPPCFATNPDC(nh2)
AuIB[T11A]GCCSYPPCFAANPDC(nh2)
AuIB[Y5A]GCCSAPPCFATNPDC(nh2)
AuIB[insC_AGAGA] cyclic GCCSYPPCFATNPDCAGAGA
AuIB[insC_AGGG] cyclicGCCSYPPCFATNPDCAGGG
AuIB[insC_AGG] cyclicGCCSYPPCFATNPDCAGG
AuIB[insC_AG] cyclicGCCSYPPCFATNPDCAG
AuIB[insC_A] cyclicGCCSYPPCFATNPDCA
AuIB[insC_GAGAAG] cyclicGCCSYPPCFATNPDCGAGAAG
AuIB[insC_GGAAAGG] cyclicGCCSYPPCFATNPDCGGAAAGG
AuIB[insC_GGAAGG] cyclicGCCSYPPCFATNPDCGGAAGG
AuIB[insC_GGAAG] cyclicGCCSYPPCFATNPDCGGAAG
AuIB[insC_GGAA] cyclicGCCSYPPCFATNPDCGGAA

References
Dutton,J.L., Bansal,P.S., Hogg,R.C., Adams,D.J., Alewood,P.F. and Craik,D.J. (2002) A New Level of Conotoxin Diversity, a Non-native Disulfide Bond Connectivity in alpha -Conotoxin AuIB Reduces Structural Definition but Increases Biological Activity J. Biol. Chem. 277:48849-48857
Luo,S., Kulak,J.M., Cartier,G.E., Jacobsen,R.B., Yoshikami,D., Olivera,B.M. and McIntosh,J.M. (1998) alpha-conotoxin AuIB selectively blocks alpha3 beta4 nicotinic acetylcholine receptors and nicotine-evoked norepinephrine release J. Neurosci. 18:8571-8579
Cho,J.H., Mok,K.H., Olivera,B.M., McIntosh,J.M., Park,K.H. and Han,K.H. (2000) Nuclear magnetic resonance solution conformation of alpha-conotoxin AuIB, an alpha(3)beta(4) subtype-selective neuronal nicotinic acetylcholine receptor antagonist J. Biol. Chem. 275:8680-8685
Lovelace,E.S., Gunasekera,S., Alvarmo,C., Clark,R.J., Nevin,S.T., Grishin,A.A., Adams,D.J., Craik,D.J., and Daly,N.L. (2011) Stabilization of α-conotoxin AuIB: influences of disulfide connectivity and backbone cyclization. Antioxid. Redox Signal. 14:87-95
Klimis,H., Adams,D.J., Callaghan,B., Nevin,S., Alewood,P.F., Vaughan,C.W., Mozar,C.A. and Christie,M.J. (2011) A novel mechanism of inhibition of high-voltage activated calcium channels by α-conotoxins contributes to relief of nerve injury-induced neuropathic pain. Pain 152:259-266
Grishin,A.A., Wang,C.I., Muttenthaler,M., Alewood,P.F., Lewis,R.J. and Adams,D.J. (2010) Alpha-conotoxin AuIB isomers exhibit distinct inhibitory mechanisms and differential sensitivity to stoichiometry of alpha3beta4 nicotinic acetylcholine receptors. J. Biol. Chem. 285:22254-22263
Napier,I.A., Klimis,H., Rycroft,B.K., Jin,A.H., Alewood,P.F., Motin,L., Adams,D.J. and Christie,M.J. (2012) Intrathecal α-conotoxins Vc1.1, AuIB and MII acting on distinct nicotinic receptor subtypes reverse signs of neuropathic pain. Neuropharmacology 62:2202-2207
Nicke,A., Samochocki,M., Loughnan,M.L., Bansal,P.S., Maelicke,A. and Lewis,R.J. (2003) Alpha-conotoxins EpI and AuIB switch subtype selectivity and activity in native versus recombinant nicotinic acetylcholine receptors. FEBS Lett. 554:219-223
Tabassum, N., Tae, H.S., Jia, X., Kaas, Q., Jiang, T., Adams, D.J. and Yu, R. (2017) Role of CysI-CysIII Disulfide Bond on the Structure and Activity of α-Conotoxins at Human Neuronal Nicotinic Acetylcholine Receptors ACS omega 2:4621-4631
Wu, X., Tae, H.S., Huang, Y.H., Adams, D.J., Craik, D.J. and Kaas, Q. (2018) Stoichiometry dependent inhibition of rat α3β4 nicotinic acetylcholine receptor by the ribbon isomer of α-conotoxin AuIB Biochemical pharmacology 155:288-297

Internal links
Protein Precursor AuIB precursor (2879)
Nucleic acids
Structure SOLUTION STRUCTURE OF ALPHA-CONOTOXIN AUIB
SOLUTION CONFORMATION OF A-CONOTOXIN AUIB

External links
Ncbi 1DG2_A, 1MXN_A, 1MXP_A, P56640

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