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

Sequence

GCCSYPPCFATNPDC(nh2)

Modified residues

position	symbol	name
16	nh2	C-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

Target	Organism		IC50		n_hill	Agonist	Ref
α1β1γδ	M. musculus		>75uM			1uM Ach	Luo,S. et al. (1998)
α2β2	R. norvegicus		>75uM			300uM Ach	Luo,S. et al. (1998)
α2β4	R. norvegicus		>75uM			300uM Ach	Luo,S. et al. (1998)
α3β2	R. norvegicus		>75uM			300uM Ach	Luo,S. et al. (1998)
α3β4	R. norvegicus	(a3b4 ratio 10:1)	2.36uM		1.68	500uM Ach	Grishin,A.A. et al. (2010)
		(a3b4 ratio 10:1)	1.1uM		1.38	50uM Ach	Grishin,A.A. et al. (2010)
			750nM		1.05	300uM Ach	Luo,S. et al. (1998)
			9.1uM			100nM epibatidine	Armishaw,C.J. et al. (2011)
		(a3b4 ratio 1:10)	3.0uM		1	50uM Ach	Grishin,A.A. et al. (2010)
			966 nM		1.1	100 μM ACh	Nicke,A. et al. (2003)
			2.5uM	+/-0.6	1.5	50-100uM Ach	Lovelace,E.S. et al. (2011)
		(a3b4 ratio 10:1)	860nM		1.37	175uM Ach	Grishin,A.A. et al. (2010)
		(a3b4 ratio 1:10)	5.8uM		1.63	5mM Ach	Grishin,A.A. et al. (2010)
		(a3b4 ratio 1:10)	1.24uM		0.85	5uM Ach	Grishin,A.A. et al. (2010)
α4β2	R. norvegicus		>75uM			300uM Ach	Luo,S. et al. (1998)
			>300uM			100nM epibatidine	Armishaw,C.J. et al. (2011)
α4β4	R. norvegicus		>75uM			300uM Ach	Luo,S. et al. (1998)
α7	R. norvegicus		>300uM			100nM epibatidine	Armishaw,C.J. et al. (2011)
			~7.5uM			1mM Ach	Luo,S. et al. (1998)
α9α10	Unknown		>1uM			30uM Ach	Klimis,H. et al. (2011)

Target	Organism		% inhibition		Concentration	Agonist	Ref
α3β4	R. norvegicus	(Adapted from reported "relative current amplitude". Error recorded as S.E. not S.D. )	85	+/-7	10 uM	2.5 mM ACh	Grishin,A.A. et al. (2013)
		([Q198A]Î±3 mutant receptor. Adapted from reported "relative current amplitude". Error recorded as S.)	75	+/-2	10 uM	50 uM ACh	Grishin,A.A. et al. (2013)
		(Adapted from reported "relative current amplitude". Error recorded as S.E. not S.D. )	49	+/-7	3 uM	50 uM ACh	Grishin,A.A. et al. (2013)
			95		10uM	50-100uM Ach	Lovelace,E.S. et al. (2011)
		([W59A]Î²4 mutant receptor. Adapted from reported "relative current amplitude". Error recorded as S.E)	11	+/-5	10 uM	2.5 mM ACh	Grishin,A.A. et al. (2013)
			0		0	100nM epibatidine	Armishaw,C.J. et al. (2011)
		([W59A/K61A]Î²4 mutant receptor. Adapted from reported "relative current amplitude". Error= S.E.)	11	+/-8	10 uM	2.5 mM ACh	Grishin,A.A. et al. (2013)
		([K61A]Î²4 mutant receptor. Adapted from reported "relative current amplitude". Error recorded as S.E)	34	+/-3	10 uM	2.5 mM ACh	Grishin,A.A. et al. (2013)
		(Adapted from reported "relative current amplitude". Error recorded as S.E. not S.D. )	83	+/-2	10 uM	50 uM ACh	Grishin,A.A. et al. (2013)
			50			Ach (3 uM)	Wu et al. (2018)
			95			Ach (100 uM)	Wu et al. (2018)
α4β2	R. norvegicus		0		0	100nM epibatidine	Armishaw,C.J. et al. (2011)
α7	R. norvegicus		0		0	100nM epibatidine	Armishaw,C.J. et al. (2011)
α9α10	Unknown		0		3uM	30uM Ach	Klimis,H. et al. (2011)

Synthetic variants

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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