AuIB (P00095) Protein Card

General Information
Name AuIB
Alternative name(s) Au1b
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. norvegicus750nM1.05300uM AchLuo,S. et al. (1998)
(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)
(a3b4 ratio 1:10)3.0uM150uM AchGrishin,A.A. et al. (2010)
9.1uM100nM epibatidineArmishaw,C.J. et al. (2011)
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)
966 nM1.1100 μM AChNicke,A. et al. (2003)
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)
9510uM50-100uM AchLovelace,E.S. et al. (2011)
([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)
00100nM epibatidineArmishaw,C.J. 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)
([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)
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 isoform]GCCSYPPCFATNPDC(nh2)
[F9A]AuIBGCCSYPPCAATNPDC
[F9G]AuIBGCCSYPPCGATNPDC
[F9H]AuIBGCCSYPPCHATNPDC
[F9NAL]AuIBGCCSYPPCXATNPDC
[F9W]AuIBGCCSYPPCWATNPDC
[F9Y]AuIBGCCSYPPCYATNPDC
[G1A]AuIBACCSYPPCFATNPDC
[P6A]AuIBGCCSYAPCFATNPDC
[Y5A]AuIBGCCSAPPCFATNPDC
cAuIB-1GCCSYPPCFATNPDCA
cAuIB-2GCCSYPPCFATNPDCAG
cAuIB-3GCCSYPPCFATNPDCAGG
cAuIB-4 (AGGG)GCCSYPPCFATNPDCAGGG
cAuIB-4 (GGAA)GCCSYPPCFATNPDCGGAA
cAuIB-5 (AGAGA)GCCSYPPCFATNPDCAGAGA
cAuIB-5 (GGAAG)GCCSYPPCFATNPDCGGAAG
cAuIB-6 (GAGAAG)GCCSYPPCFATNPDCGAGAAG
cAuIB-6 (GGAAGG)GCCSYPPCFATNPDCGGAAGG
cAuIB-7 (GGAAAGG)GCCSYPPCFATNPDCGGAAAGG

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

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 P56640, 1MXP_A, 1MXN_A, 1DG2_A

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