LsIA (P06776) Protein Card

General Information

Name	LsIA
Alternative name(s)	gLsIA
Organism	Conus limpusi
Organism region	Indo-Pacific
Organism diet	vermivorous
Protein Type	Wild type

Classification

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

Sequence

SGCCSNPACRVNNPNIC(nh2)

Modified residues

position	symbol	name
18	nh2	C-term amidation

Sequence evidence

protein level

Average Mass

1746.96

Monoisotopic Mass

1745.68

Isoelectric Point

10.94

Extinction Coefficient [280nm]

Activity

IC50: Nicotinic acetylcholine receptors

Target	Organism	IC50		n_hill	Agonist	Ref
α3α5β2	R. norvegicus	31.2 nM	+/-5.6	-1.1	50 uM Ach	Inserra,M.C. et al. (2013)
α3β2	R. norvegicus	10.3 nM	[8.8-12.1]	-1.3	50 uM Ach	Inserra,M.C. et al. (2013)
α3β4	H. sapiens	>10 uM			30 uM nicotine	Abraham,N. et al. (2017)
α7	H. sapiens	10.1 nM	[8.7-11.6]	-2.1	200 uM Ach	Inserra,M.C. et al. (2013)
		0.07 uM	+/-0.01		30 uM choline	Abraham,N. et al. (2017)
		0.30 uM	+/-0.06		30 uM choline	Ho,T.N.T. et al. (2021)

Ki: Nicotinic acetylcholine receptors

Target	Organism		Ki		Competitor	Agonist	Ref
α3α5β2	R. norvegicus	(50 uM Ach)	9.6 nM			50 uM Ach	Inserra,M.C. et al. (2013)
α3β2	R. norvegicus	(50 uM Ach)	15.2 nM			50 uM Ach	Inserra,M.C. et al. (2013)
α7	H. sapiens	(200 uM Ach)	1.47 nM			200 uM Ach	Inserra,M.C. et al. (2013)
AChBP	A. californica		5.44 nM	+/-0.35	epibatidine (1 nM)		Abraham,N. et al. (2017)
	L. stagnalis		17.4 uM	+/-10.7	epibatidine (1 nM)		Abraham,N. et al. (2017)
			0.21 uM	+/-0.04	epibatidine (1 nM)		Abraham,N. et al. (2017)

Percentage inhibition: Nicotinic acetylcholine receptors

Target	Organism	% inhibition		Concentration	Agonist	Ref
α3β4	R. norvegicus	40	+/-5	3 uM	50 uM Ach	Inserra,M.C. et al. (2013)
α4β2	R. norvegicus	0		3 uM	50 uM Ach	Inserra,M.C. et al. (2013)
α4β4	R. norvegicus	0		3 uM	50 uM Ach	Inserra,M.C. et al. (2013)
α9α10	R. norvegicus	0		3 uM	50 uM Ach	Inserra,M.C. et al. (2013)

Synthetic variants

LsIA deamidated	SGCCSNPACRVNNPNIC
LsIA [N12D]	SGCCSNPACRVDNPNIC(nh2)
LsIA [N12L]	SGCCSNPACRVLNPNIC(nh2)
LsIA [N12Q]	SGCCSNPACRVQNPNIC(nh2)
LsIA [N6H]	SGCCSHPACRVNNPNIC(nh2)
LsIA [R10D]	SGCCSNPACDVNNPNIC(nh2)
LsIA [R10F,N12L]	SGCCSNPACFVLNPNIC(nh2)
LsIA [R10F]	SGCCSNPACDVNNPNIC(nh2)
LsIA [R10M]	SGCCSNPACMVNNPNIC(nh2)
LsIA [del1-2]	CCSNPACRVNNPNIC(nh2)
LsIA [del1]	GCCSNPACRVNNPNIC(nh2)
LsIA[S5R]	SGCCRNPACRVNNPNIC(nh2)
LsIA[insA5]	SGCCASNPACRVNNPNIC(nh2)
LsIA[insR6]	SGCCSRNPACRVNNPNIC(nh2)

References

Inserra,M.C., Kompella,S.N., Vetter,I., Brust,A., Daly,N.L., Cuny,H., Craik,D.J., Alewood,P.F., Adams,D.J. and Lewis,R.J. (2013) Isolation and characterization of α-conotoxin LsIA with potent activity at nicotinic acetylcholine receptors. Biochem. Pharmacol. 86:791-799

Abraham,N., Healy,M., Ragnarsson,L., Brust,A., Alewood,P.F. and Lewis,R.J. (2017) Structural mechanisms for α-conotoxin activity at the human α3β4 nicotinic acetylcholine receptor. Sci Rep 7:45466

Ho,T.N.T., Abraham,N., Lewis,R.J. (2021) Rigidity of loop 1 contributes to equipotency of globular and ribbon isomers of α-conotoxin AusIA Sci Rep 11:21928

Internal links

Nucleic acids
Structure	Structural mechanisms for alpha-conotoxin selectivity at the human alpha3beta4 nicotinic acetylcholine receptor

External links

Tools