GIIIA (P01571) Protein Card

General Information
Name GIIIA
Alternative name(s) G3.9,GTx-I,Geographutoxin I,Myotoxin I
Organism Conus geographus (Geography cone)
Organism region Indo-Pacific
Organism diet piscivorous
Protein Type Wild type
Protein precursor GIIIA precursor (1464)
Notes Induce paralysis in vertebrates. Bind to tetrodotoxin sensitive Na channel (Cruz et al 1985) and, presumably, interact with site 1 in the Na channel pore. 10 μM rapidly blocks A-fiber but not C-fiber compound action potentials in mouse sciatic nerve [Wilson,M.J., Zhang,M (2015)].

Classification
Conopeptide class conotoxin
Gene superfamily M superfamily
Cysteine framework III
Pharmacological family mu conotoxin

Sequence
RDCCTOOKKCKDRQCKOQRCCA(nh2)
Modified residues
positionsymbolname
6O4-Hydroxyproline
7O4-Hydroxyproline
17O4-Hydroxyproline
23nh2C-term amidation
Sequence evidence protein level
Average Mass 2609.04
Monoisotopic Mass 2607.12
Isoelectric Point 11.87
Extinction Coefficient [280nm] NA

Activity

IC50: Voltage-Gated Sodium Channels

TargetOrganismIC50Ref
Nav1.2R. norvegicus17.8uM+/-1.7Wilson,M.J. et al. (2011)
2.7uMSafo,P. et al. (2000)
Nav1.3R. norvegicus>10uMWilson,M.J. et al. (2011)
Nav1.4R. norvegicus19nM+/-2Wilson,M.J. et al. (2011)
19nMSafo,P. et al. (2000)
Nav1.5R. norvegicus>10uMWilson,M.J. et al. (2011)
Nav1.6M. musculus680nM+/-60Wilson,M.J. et al. (2011)
Nav1.7R. norvegicus6.0uMSafo,P. et al. (2000)
>10uMWilson,M.J. et al. (2011)
Nav1.8R. norvegicus>10uMWilson,M.J. et al. (2011)

Kd: Voltage-Gated Sodium Channels

TargetOrganismKdRef
Nav1.1R. norvegicus260nM+/-90Wilson,M.J. et al. (2011)

Percentage inhibition: Voltage-Gated Sodium Channels

TargetOrganism% inhibitionConcentrationRef
Nav TTX-RR. pipiens05uMZhang,M.M. et al. (2006)

Synthetic variants
GIIIA [R13A](nh2)ACCRQOKCQADKCKKOOTCCDR
GIIIA-1(nh2)ACCRQOKAQRDKCKKOOTCADR
GIIIA-12(nh2)ACARQOKAQRDKCKKOOTAADR
GIIIA-13(nh2)AACRQOKAQRDKAKKOOTCADR
GIIIA-2(nh2)ACARQOKCQRDKCKKOOTACDR
GIIIA-23(nh2)AAARQOKCQRDKAKKOOTACDR
GIIIA-3(nh2)AACRQOKCQRDKAKKOOTCCDR

References
Safo,P., Rosenbaum,T., Shcherbatko,A., Choi,D.Y., Han,E., Toledo-Aral,J.J., Olivera,B.M., Brehm,P. and Mandel,G. (2000) Distinction among neuronal subtypes of voltage-activated sodium channels by mu-conotoxin PIIIA J. Neurosci. 20:76-80
Cruz,L.J., Gray,W.R., Olivera,B.M., Zeikus,R.D., Kerr,L., Yoshikami,D. and Moczydlowski,E. (1985) Conus geographus toxins that discriminate between neuronal and muscle sodium channels J. Biol. Chem. 260:9280-9288
Sato,S., Nakamura,H., Ohizumi,Y., Kobayashi,J. and Hirata,Y. (1983) The amino acid sequences of homologous hydroxyproline-containing myotoxins from the marine snail Conus geographus venom FEBS Lett. 155:277-280
Lancelin,J.M., Kohda,D., Tate,S., Yanagawa,Y., Abe,T., Satake,M. and Inagaki,F. (1991) Tertiary structure of conotoxin GIIIA in aqueous solution Biochemistry 30:6908-6916
Wakamatsu,K., Kohda,D., Hatanaka,H., Lancelin,J.M., Ishida,Y., Oya,M., Nakamura,H., Inagaki,F. and Sato,K. (1992) Structure-activity relationships of mu-conotoxin GIIIA: structure determination of active and inactive sodium channel blocker peptides by NMR and simulated annealing calculations Biochemistry 31:12577-12584
Safavi-Hemami,H., Siero,W.A., Kuang,Z., Williamson,N.A., Karas,J.A., Page,L.R., MacMillan,D., Callaghan,B., Kompella,S.N., Adams,D.J., Norton,R.S., and Purcell,A.W. (2011) Embryonic toxin expression in the cone snail Conus victoriae: primed to kill or divergent function? J. Biol. Chem. 286:22546-22557
Wilson,M.J., Yoshikami,D., Azam,L., Gajewiak,J., Olivera,B.M., Bulaj,G. and Zhang,M.M. (2011) μ-Conotoxins that differentially block sodium channels NaV1.1 through 1.8 identify those responsible for action potentials in sciatic nerve. Proc. Natl. Acad. Sci. U.S.A. 108:10302-10307
Wilson,M.J., Zhang,M.M., Gajewiak,J., Azam,L., Rivier,J.E., Olivera,B.M. and Yoshikami,D. (2015) Α- and β-subunit composition of voltage-gated sodium channels investigated with μ-conotoxins and the recently discovered μO§-conotoxin GVIIJ. J. Neurophysiol. 113:2289-2301

Internal links
Protein Precursor GIIIA precursor (1464)
Nucleic acids
Structure STRUCTURE-ACTIVITY RELATIONSHIPS OF MU-CONOTOXIN GIIIA: STRUCTURE DETERMINATION OF ACTIVE AND INACTIVE SODIUM CHANNEL BLOCKER PEPTIDES BY NMR AND SIMULATED ANNEALING CALCULATIONS
STRUCTURE-ACTIVITY RELATIONSHIPS OF MU-CONOTOXIN GIIIA: STRUCTURE DETERMINATION OF ACTIVE AND INACTIVE SODIUM CHANNEL BLOCKER PEPTIDES BY NMR AND SIMULATED ANNEALING CALCULATIONS
Conotoxin GIIIA
Conotoxin GIIIA

External links
Ncbi 1TCJ_A, 1TCG_A

Tools