PIA (P00595) Protein Card

General Information
Name PIA
Alternative name(s) P1a
Organism Conus purpurascens
Organism region Eastern Pacific
Organism diet piscivorous
Protein Type Wild type
Protein precursor PIA precursor (410)
PIA precursor (3011)

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

Sequence
RDPCCSNPVCTVHNPQIC(nh2)
Modified residues
positionsymbolname
19nh2C-term amidation
Sequence evidence nucleic acid level
Average Mass 1981.26
Monoisotopic Mass 1979.82
Isoelectric Point 7.88
Extinction Coefficient [280nm] NA

Activity

IC50: Nicotinic acetylcholine receptors

TargetOrganismIC50nhillAgonistRef
α1β1δεH. sapiens>10uM10uM AChDowell,C. et al. (2003)
α2β2R. norvegicus>10uM100uM AChDowell,C. et al. (2003)
α2β4R. norvegicus >10uM 100uM AChDowell,C. et al. (2003)
α3β2R. norvegicus74nM+/-360.8100uM AChDowell,C. et al. (2003)
α3β4R. norvegicus518nM+/-2000.93100uM AChDowell,C. et al. (2003)
α4β2R. norvegicus >10uM100uM AChDowell,C. et al. (2003)
α4β4R. norvegicus >10uM 100uM AChDowell,C. et al. (2003)
α6β4R. norvegicus33nM+/-161.1100uM AChDowell,C. et al. (2003)
α6/α3β2R. norvegicus690pM+/-3000.81100uM AChDowell,C. et al. (2003)
α6/α3β2β3H. sapiens1.7nM+/-10.98100uM AChDowell,C. et al. (2003)
R. norvegicus950pM+/-3501.1100uM AChDowell,C. et al. (2003)
α6/α3β4H. sapiens12.6nM+/-61.2100uM AChDowell,C. et al. (2003)
R. norvegicus30nM+/-170.93100uM AChDowell,C. et al. (2003)

Ki: Nicotinic acetylcholine receptors

TargetOrganismKiCompetitorAgonistRef
a7*α6β2*R. norvegicus(Low affinity site)35uM 0.1nM epibatidinePucci,L. et al. (2011)
(High affinity site)32nM0.1nM epibatidinePucci,L. et al. (2011)

Synthetic variants
PIA Δ1DPCCSNPVCTVHNPQIC(nh2)
PIA Δ1-2PCCSNPVCTVHNPQIC(nh2)
PIA Δ1-3CCSNPVCTVHNPQIC(nh2)
PIA [R1ADMA](ADMA)DPCCSNPVCTVHNPQIC(nh2)
PIA [R1E]EDPCCSNPVCTVHNPQIC(nh2)
PIA [R1K]KDPCCSNPVCTVHNPQIC(nh2)
PIA [R1L]LDPCCSNPVCTVHNPQIC(nh2)

References
Dowell,C., Olivera,B.M., Garrett,J.E., Staheli,S.T., Watkins,M., Kuryatov,A., Yoshikami,D., Lindstrom,J.M. and McIntosh,J.M. (2003) Alpha-conotoxin PIA is selective for alpha6 subunit-containing nicotinic acetylcholine receptors J. Neurosci. 23:8445-8452
Chi,S.W., Lee,S.H., Kim,D.H., Kim,J.S., Olivera,B.M., McIntosh,J.M. and Han,K.H. (2005) Solution structure of alpha-conotoxin PIA, a novel antagonist of alpha6 subunit containing nicotinic acetylcholine receptors Biochem. Biophys. Res. Commun. 338:1990-1997
Pucci,L., Grazioso,G., Dallanoce,C., Rizzi,L., De Micheli,C., Clementi,F., Bertrand,S., Bertrand,D., Longhi,R., De Amici,M. and Gotti,C. (2011) Engineering of α-conotoxin MII-derived peptides with increased selectivity for native α6β2* nicotinic acetylcholine receptors. FASEB J. 25:3775-3789
Himaya, S.W.A., Mari, F. and Lewis, R.J. (2018) Accelerated proteomic visualization of individual predatory venoms of Conus purpurascens reveals separately evolved predation-evoked venom cabals Scientific reports 8:1-8

Internal links
Protein Precursor PIA precursor (410)
PIA precursor (3011)
Nucleic acids
Structure SOLUTION CONFORMATION OF ALPHA-CONOTOXIN PIA

External links
Ncbi 1ZLC_A

Tools