PeIA (P02608) Protein Card

General Information
Name PeIA
Alternative name(s) Pe1a
Organism Conus pergrandis
Organism region Indo-Pacific
Protein Type Wild type
Protein precursor PeIA precursor (5)
Notes Inhibition of N-type Ca2+ channel current through the GABAB in rat DRG neurons with an IC50 of 1.1nM (Daly et al.). The specific targeted molecule remains unclear.

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

Sequence
GCCSHPACSVNHPELC(nh2)
Modified residues
positionsymbolname
17nh2C-term amidation
Sequence evidence nucleic acid level
Average Mass 1651.86
Monoisotopic Mass 1650.62
Isoelectric Point 6.81
Extinction Coefficient [280nm] NA

Activity

IC50: Nicotinic acetylcholine receptors

TargetOrganismIC50nhillAgonistRef
α1β1γδM. musculus>1uMAchDaly,N.L. et al. (2011)
α3β2R. norvegicus23nM+/-51.2510uM AChMcIntosh,J.M. et al. (2005)
9.7nM+/-2100uM AchHone,A.J. et al. (2012)
97.5nM+/-10.90.8100uM AchDaly,N.L. et al. (2011)
19.2 nM+/-2.1100 uM AchHone,A.J. et al. (2013)
α3β4R. norvegicus1.5uM+/-0.2100uM AchHone,A.J. et al. (2012)
480nM+/-1601.23100uM AChMcIntosh,J.M. et al. (2005)
α4β2R. norvegicus11.6uM+/-3.63.0210uM AChMcIntosh,J.M. et al. (2005)
>1uM100uM AchDaly,N.L. et al. (2011)
α6β4R. norvegicus262 nM+/-70100uM AchHone,A.J. et al. (2013)
α6/α3β2β3H. sapiens16 nM [14.2-18.1]100 uM AchHone et al. (2018)
R. norvegicus17.2 nM+/-1.8100uM AchHone,A.J. et al. (2013)
16.3 nM[13.2-20.2]100 uM AchHone et al. (2018)
11.1nM+/-3.9100uM AchHone,A.J. et al. (2012)
α6/α3β4H. sapiens9.9 nM[8.2-11.9]300uM AchHone et al. (2018)
R. norvegicus154 nM[143-166]300uM AchHone et al. (2018)
148nM+/-28100uM AchHone,A.J. et al. (2012)
α7H. sapiens>1uM200uM AchDaly,N.L. et al. (2011)
R. norvegicus1.8uM+/-0.41.1100uM AChMcIntosh,J.M. et al. (2005)
α9α10R. norvegicus33nM+/-5100uM AchHone,A.J. et al. (2012)
6.9nM+/-2.60.8810uM AChMcIntosh,J.M. et al. (2005)
54.9nM+/-90.630uM AchDaly,N.L. et al. (2011)

Synthetic variants
PeIA[A7V,S9H,V10A,N11R,E14A]GCCSHPVCHARHPALC(nh2)
PeIA[A7V,S9H,V10A,N11R]GCCSHPVCHARHPELC(nh2)
PeIA[A7V]GCCSHPVCSVNHPELC(nh2)
PeIA[E14A]GCCSHPACSVNHPALC(nh2)
PeIA[E14N]GCCSHPACSVNHPNLC(nh2)
PeIA[H12A]GCCSHPACSVNAPELC(nh2)
PeIA[H5A]GCCSAPACSVNHPELC(nh2)
PeIA[H5N]GCCSNPACSVNHPELC(nh2)
PeIA[L15A]GCCSHPACSVNHPEAC(nh2)
PeIA[N11A]GCCSHPACSVAHPELC(nh2)
PeIA[N11E]GCCSHPACSVEHPELC(nh2)
PeIA[N11K]GCCSHPACSVKHPELC(nh2)
PeIA[N11R]GCCSHPACSVRHPELC(nh2)
PeIA[P13A]GCCSHPACSVNHAELC(nh2)
PeIA[P13O]GCCSHPACSVNHOELC(nh2)
PeIA[P13Q]GCCSHPACSVNHQELC(nh2)
PeIA[P13R]GCCSHPACSVNHRELC(nh2)
PeIA[P13S]GCCSHPACSVNHSELC(nh2)
PeIA[P6A]GCCSHAACSVNHPELC(nh2)
PeIA[P6O]GCCSHOACSVNHPELC(nh2)
PeIA[S4A]GCCAHPACSVNHPELC(nh2)
PeIA[S9A]GCCSHPACAVNHPELC(nh2)
PeIA[S9H,V10A,N11R,E14A]GCCSHPACHARHPALC(nh2)
PeIA[S9H,V10A,N11R]GCCSHPACHARHPELC(nh2)
PeIA[S9H]GCCSHPACHVNHPELC(nh2)
PeIA[S9R]GCCSHPACRVNHPELC(nh2)
PeIA[V10A]GCCSHPACSANHPELC(nh2)
PeIA[V10L]GCCSHPACSLNHPELC(nh2)
PeIA[V10R]GCCSHPACSRNHPELC(nh2)

References
McIntosh,J.M., Plazas,P.V., Watkins,M., Gomez-Casati,M.E., Olivera,B.M. and Elgoyhen,A.B. (2005) A novel alpha-conotoxin, PeIA, cloned from Conus pergrandis, discriminates between rat alpha9alpha10 and alpha7 nicotinic cholinergic receptors J. Biol. Chem. 280:30107-30112
Daly,N.L., Callaghan,B., Clark,R.J., Nevin,S.T., Adams,D.J. and Craik,D.J. (2011) Structure and activity of alpha-conotoxin PeIA at nicotinic acetylcholine receptor subtypes and GABA(B) receptor-coupled N-type calcium channels. J. Biol. Chem. 286:10233-10237
Hone,A.J., Scadden,M., Gajewiak,J., Christensen,S., Lindstrom,J. and McIntosh,J.M. (2012) α-Conotoxin PeIA[S9H,V10A,E14N] potently and selectively blocks α6β2β3 versus α6β4 nicotinic acetylcholine receptors. Mol. Pharmacol. 82:972-982
Hone,A.J., Ruiz,M., Scadden,M., Christensen,S., Gajewiak,J., Azam,L. and McIntosh,J.M. (2013) Positional scanning mutagenesis of α-conotoxin PeIA identifies critical residues that confer potency and selectivity for α6/α3β2β3 and α3β2 nicotinic acetylcholine receptors. J. Biol. Chem. 288:25428-25439
Hone, A.J., Talley, T.T., Bobango, J., Melo, C.H., Hararah, F., Gajewiak, J., Christensen, S., Harvey, P.J., Craik, D.J. and McIntosh, J.M. (2018) Molecular determinants of α-conotoxin potency for inhibition of human and rat α6β4 nicotinic acetylcholine receptors Journal of Biological Chemistry 293:17838-17852

Internal links
Protein Precursor PeIA precursor (5)
Nucleic acids
Structure NMR structure of PeIA
Crystal structure of acetylcholine binding protein (AChBP) from Aplysia Californica in complex with alpha-conotoxin PeIA

External links
Ncbi AAY57814, Q1L777

Tools