GVIIJ[(Btr)2W,(Scc)24(Sgc)] (P06834) Protein Card

General Information
Name GVIIJ[(Btr)2W,(Scc)24(Sgc)] (named by ConoServer)
Alternative name(s) GVIIJ[SSG]
Organism synthetic construct
Protein Type Synthetic
Parent GVIIJ
Notes

Blocks I(Na) in small but not large rat dorsal root ganglia neuron [Wilson, M.J., Zhang, M. (2015)].

Does not block A-fiber or C-fiber compound action potentials in mouse and rat sciatic nerves [Wilson, M.J., Zhang, M. (2015)].

Block of rNav1.2[C912A] or [C918A] mutants is rapidly reversible. +DTT it is slowly reversible [Zhang,M.M., Gajewiak (2015)].

Rate of block of rNav1.4 is unaffected by μ-PIIIA[R14Q], indicating that this peptide may bind independently of site 1. [Green, B.R. et al. (2016)]

Classification
Conopeptide class conotoxin
Gene superfamily
Cysteine framework VI/VII
Pharmacological family mu conotoxin

Sequence
GWCGDOGATCGKLRLYCCSGFCD(Sgc)YTKTCKDKSSA
Modified residues
positionsymbolname
6O4-Hydroxyproline
24SgcGlutathionylated cysteine
Sequence evidence protein level
Average Mass 4044.52
Monoisotopic Mass 4041.57
Isoelectric Point 10.68
Extinction Coefficient [280nm] 8480.00

Activity

IC50: Voltage-Gated Sodium Channels

TargetOrganismIC50Ref
Nav1.2H. sapiens(Expressed in HEK 293 cells)1110 nM+/-372Gajewiak,J. et al. (2014)
R. norvegicus(Mutant: Nav1.2[C910L]. Expressed in X. laevis oocytes)88 μM+/-2Gajewiak,J. et al. (2014)
Nav1.4H. sapiens(Expressed in HEK 293 cells)812 nM+/-515Gajewiak,J. et al. (2014)
Nav1.5R. norvegicus(Expressed in X. laevis oocytes)207 μM+/-12Gajewiak,J. et al. (2014)
Nav1.6H. sapiens(Expressed in CHO cells)756 nM+/-62Gajewiak,J. et al. (2014)
Nav1.7H. sapiens(Expressed in HEK 293 cells)783 nM+/-110Gajewiak,J. et al. (2014)

Kd: Voltage-Gated Sodium Channels

TargetOrganismKdRef
Nav1.1R. norvegicus(Expressed in X. laevis oocytes)0.011 μM+/-0.002Gajewiak,J. et al. (2014)
Nav1.2R. norvegicus(Expressed in X. laevis oocytes)0.011 μM+/-0.006Gajewiak,J. et al. (2014)
Nav1.3R. norvegicus(Expressed in X. laevis oocytes)0.015 μM+/-0.006Gajewiak,J. et al. (2014)
Nav1.4R. norvegicus(Expressed in X. laevis oocytes)0.0047 μM+/-0.0024Gajewiak,J. et al. (2014)
Nav1.5R. norvegicus(Mutant: Nav1.5[L869C]. Expressed in X. laevis oocytes)0.13 μM+/-0.09Gajewiak,J. et al. (2014)
Nav1.6R. norvegicus(Expressed in X. laevis oocytes)0.36 μM+/-0.05Gajewiak,J. et al. (2014)
Nav1.7R. norvegicus(Expressed in X. laevis oocytes)0.041 μM+/-0.027Gajewiak,J. et al. (2014)
(With β1 subunit. Expressed in X. laevis oocytes)0.045 μM+/-0.038Gajewiak,J. et al. (2014)
(With β3 subunit. Expressed in X. laevis oocytes)0.05 μM+/-0.023Gajewiak,J. et al. (2014)

Percentage inhibition: Voltage-Gated Sodium Channels

TargetOrganism% inhibitionConcentrationRef
Nav1.2R. norvegicus(Expressed in X. laevis oocytes.)73+/-1033 μMZhang,M.M. et al. (2015)
(Mutant: Nav1.2[C918A]. Expressed in X. laevis oocytes.)20+/-333 μMZhang,M.M. et al. (2015)
(Mutant: Nav1.2[C912A]. Expressed in X. laevis oocytes.)73+/-1133 μMZhang,M.M. et al. (2015)
Nav1.5H. sapiens(Expressed in HEK 293 cells)19+/-210 μMGajewiak,J. et al. (2014)
Nav1.8R. norvegicus(No activity)0Gajewiak,J. et al. (2014)

References
Gajewiak,J., Azam,L., Imperial,J., Walewska,A., Green,B.R., Bandyopadhyay,P.K., Raghuraman,S., Ueberheide,B., Bern,M., Zhou,H.M., Minassian,N.A., Hagan,R.H., Flinspach,M., Liu,Y., Bulaj,G., Wickenden,A.D., Olivera,B.M., Yoshikami,D. and Zhang,M.M. (2014) A disulfide tether stabilizes the block of sodium channels by the conotoxin μO§-GVIIJ. Proc. Natl. Acad. Sci. U.S.A. 111:2758-2763
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
Zhang,M.M., Gajewiak,J., Azam,L., Bulaj,G., Olivera,B.M. and Yoshikami,D. (2015) Probing the Redox States of Sodium Channel Cysteines at the Binding Site of μO§-Conotoxin GVIIJ. Biochemistry 54:3911-3920
Green,B.R., Gajewiak,J., Chhabra,S., Skalicky,J.J., Zhang,M.M., Rivier,J.E., Bulaj,G., Olivera,B.M., Yoshikami,D. and Norton,R.S. (2016) Structural Basis for the Inhibition of Voltage-gated Sodium Channels by Conotoxin μO§-GVIIJ. J. Biol. Chem. 291:7205-7220

Internal links
Nucleic acids
Structure

External links

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