RgIA (P02585) Protein Card

General Information
Name RgIA
Alternative name(s) Rg1a
Organism Conus regius
Organism region Eastern Pacific
Organism diet vermivorous
Protein Type Wild type
Protein precursor RgIA precursor (593)
Notes This protein sequence has been predicted from the protein prosequence (Ellison et al. 2006). The final arginine is usually cleaved by an enzyme (CPE). The sequence Reg1e, a protein directly purified from the venom duct, seems to be the real mature peptide corresponding to the precursor sequence (it presents an hydroxyproline, a N-terminal amidation and does not have the arginine).

Inhibition of N-type Ca2+ channel current through the GABAB in a9 KO mouse DRG neurons with an IC50 of 22.4 nM (Callaghan et al.). The specific receptor remains unclear. Inhibited HVA Ca2+ channel current via GABAB receptors in rat DRG neurons with an IC50 of 14.7 nM. (Halai 2011)


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

Sequence
GCCSDPRCRYRCR
Sequence evidence nucleic acid level
Average Mass 1570.79
Monoisotopic Mass 1569.62
Isoelectric Point 12.50
Extinction Coefficient [280nm] 1490.00

Activity

IC50: Nicotinic acetylcholine receptors

TargetOrganismIC50nhillAgonistRef
α1β1δεH. sapiens16uM10uM AchVincler,M. et al. (2006)
α2β2R. norvegicus>10uM100 uM AchEllison,M. et al. (2006)
α2β4R. norvegicus>10uM100 uM AchEllison,M. et al. (2006)
α3β2R. norvegicus>10uM100 uM AchEllison,M. et al. (2006)
α3β4R. norvegicus>10uM100 uM AchEllison,M. et al. (2006)
α4β2R. norvegicus>10uM100 uM AchEllison,M. et al. (2006)
α4β4R. norvegicus>10uM100 uM AchEllison,M. et al. (2006)
α6/α3β2β3R. norvegicus>10uM100 uM AchEllison,M. et al. (2006)
α6/α3β4R. norvegicus>10uM100 uM AchVincler,M. et al. (2006)
α7R. norvegicus4.66uM1.2200 uM AchEllison,M. et al. (2006)
3.31uM0.9200uM AchEllison,M. et al. (2008)
α9α10R. norvegicus(plus BAPTA)5.19nM1.210uM AchEllison,M. et al. (2006)
4.55nM1.110uM AchEllison,M. et al. (2006)
(minus BAPTA)3.60nM0.9810uM AchEllison,M. et al. (2006)
8.47nM1.350uM AchEllison,M. et al. (2008)
5.2nM10uM AchVincler,M. et al. (2006)
unidentified(nAChR was hybrid human α9/rat α10. 95% confidence interval IC50 = 28-59 nM )40 nM50 uM? AchHalai,R. et al. (2011)

Percentage inhibition: Nicotinic acetylcholine receptors

TargetOrganism% inhibitionConcentrationRef
α9α10unidentified(nAChR was hybrid human α9/rat α10. )60+/-450 nMHalai,R. et al. (2011)

Synthetic variants
RgIA [Cys2Agl,Cys8Agl]G(Agl)CSDPR(Agl)RYRCR
RgIA [Cys3Agl,Cys12Agl]GC(Agl)SDPRCRYR(Agl)R
RgIA [D5E]GCCSEPRCRYRCR
RgIA [P6V]GCCSDVRCRYRCR
RgIA [R7K]GCCSDPKCRYRCR
RgIA [R9A]GCCSDPRCAYRCR
RgIA [S4A]GCCADPRCRYRCR
RgIA [Y10W]GCCSDPRCRWRCR
RgIA[deltaR]GCCSDPRCRYRC(nh2)
cRgIA-3GCCSDPRCRYRCGAA
cRgIA-4GCCSDPRCRYRCGAAG
cRgIA-5GCCSDPRCRYRCGAAGG
cRgIA-6GCCSDPRCRYRCGGAAGG
cRgIA-7GCCSDPRCRYRCGGAAGAG

References
Ellison,M., Haberlandt,C., Gomez-Casati,M.E., Watkins,M., Elgoyhen,A.B., McIntosh,J.M. and Olivera,B.M. (2006) Alpha-RgIA: a novel conotoxin that specifically and potently blocks the alpha9alpha10 nAChR Biochemistry 45:1511-1517
Ellison,M., Feng,Z.P., Park,A.J., Zhang,X., Olivera,B.M., McIntosh,J.M. and Norton,R.S. (2008) Alpha-RgIA, a novel conotoxin that blocks the alpha9alpha10 nAChR: structure and identification of key receptor-binding residues. J. Mol. Biol. 377:1216-1227
Cuny,H., Kompella,S.N., Tae,H.S., Yu,R. and Adams,D.J. (2016) Key Structural Determinants in the Agonist Binding Loops of Human β2 and β4 Nicotinic Acetylcholine Receptor Subunits Contribute to α3β4 Subtype Selectivity of α-Conotoxins. J. Biol. Chem. 291:23779-23792
Halai,R., Callaghan,B., Daly,N.L., Clark,R.J., Adams,D.J. and Craik,D.J. (2011) Effects of cyclization on stability, structure, and activity of α-conotoxin RgIA at the α9α10 nicotinic acetylcholine receptor and GABA(B) receptor. J. Med. Chem. 54:6984-6992

Internal links
Protein Precursor RgIA precursor (593)
Nucleic acids
Structure alpha-RgIA, a Novel Conotoxin That Blocks the alpha9alpha10 nAChR
Solution structure of RgIA

External links
Ncbi P0C1D0, ABB55879

Tools