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
positionsymbolname
18nh2C-term amidation
Sequence evidence protein level
Average Mass 1746.96
Monoisotopic Mass 1745.68
Isoelectric Point 10.94
Extinction Coefficient [280nm] NA

Activity

IC50: Nicotinic acetylcholine receptors

TargetOrganismIC50nhillAgonistRef
α3α5β2R. norvegicus31.2 nM+/-5.6-1.150 uM AchInserra,M.C. et al. (2013)
α3β2R. norvegicus10.3 nM[8.8-12.1]-1.350 uM AchInserra,M.C. et al. (2013)
α3β4H. sapiens>10 uM30 uM nicotineAbraham,N. et al. (2017)
α7H. sapiens10.1 nM[8.7-11.6]-2.1200 uM AchInserra,M.C. et al. (2013)
0.07 uM+/-0.0130 uM cholineAbraham,N. et al. (2017)
0.30 uM+/-0.0630 uM cholineHo TNT et al. (2021)

Ki: Nicotinic acetylcholine receptors

TargetOrganismKiCompetitorAgonistRef
α3α5β2R. norvegicus(50 uM Ach)9.6 nM50 uM AchInserra,M.C. et al. (2013)
α3β2R. norvegicus(50 uM Ach)15.2 nM50 uM AchInserra,M.C. et al. (2013)
α7H. sapiens(200 uM Ach)1.47 nM200 uM AchInserra,M.C. et al. (2013)
AChBPA. californica5.44 nM+/-0.35epibatidine (1 nM)Abraham,N. et al. (2017)
L. stagnalis17.4 uM+/-10.7epibatidine (1 nM)Abraham,N. et al. (2017)
0.21 uM+/-0.04epibatidine (1 nM)Abraham,N. et al. (2017)

Percentage inhibition: Nicotinic acetylcholine receptors

TargetOrganism% inhibitionConcentrationAgonistRef
α3β4R. norvegicus40+/-53 uM50 uM AchInserra,M.C. et al. (2013)
α4β2R. norvegicus03 uM50 uM AchInserra,M.C. et al. (2013)
α4β4R. norvegicus03 uM50 uM AchInserra,M.C. et al. (2013)
α9α10R. norvegicus03 uM50 uM AchInserra,M.C. et al. (2013)

Synthetic variants
LsIA deamidatedSGCCSNPACRVNNPNIC
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 TNT, Abraham N, Lewis RJ (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