GeXIVA[ribbon] (P05344) Protein Card

General Information
Name GeXIVA[ribbon] (named by ConoServer)
Alternative name(s) Ge14a,GeXIVA[1-4]
Organism Conus generalis
Organism region Indo-Pacific
Organism diet vermivorous
Protein Type Wild type
Protein precursor GeXIVA precursor (5224)
Notes

GeXIVA inhibits Sf9 cell growth (Gao et al., 2013). There is a discrepancy in the sequence initally published in GenBank in 2012 and the sequence published in peer-reviewed journals (involving the same authors).

Yousuf et al. (2021) discovered that GeXIVA[ribbon] does not affect the membrane excitability of mouse DRG neurons, and inhibits Cav2.2 through the GABAB receptor pathway.


Classification
Conopeptide class conotoxin
Gene superfamily O1 superfamily
Cysteine framework XIV
Pharmacological family alpha conotoxin

Sequence
TCRSSGRYCRSPYDRRRRYCRRITDACV
Sequence evidence protein level
Average Mass 3452.92
Monoisotopic Mass 3450.62
Isoelectric Point 12.80
Extinction Coefficient [280nm] 4470.00

Activity

IC50: Nicotinic acetylcholine receptors

TargetOrganismIC50nhillAgonistRef
α1β1δεM. musculus840 nM[583-1206]Ach (10 uM)Xu et al. (2020)
α2β2R. norvegicus440 nM[335-575]Ach (100 uM)Xu et al. (2020)
α3β2R. norvegicus1250 nM[782-1991]Ach (100 uM)Xu et al. (2020)
α3β4R. norvegicus3400 nM[1279-9048]Ach (100 uM)Xu et al. (2020)
α6/α3β4R. norvegicus1110 nM[30-1949]Ach (100 uM)Xu et al. (2020)
α7R. norvegicus2830 nM[1910-4188]Ach (200 uM)Xu et al. (2020)
α9α10H. sapiens35.1 nM+/-2.7Ach (6 uM)Wu X et al. (2017)
R. norvegicus7 nM[3.6-13.4]Ach (10 uM)Luo,S. et al. (2015)
7.0 nM[3.6-13.4]0.79Ach (10 uM)Luo,S. et al. (2015)
16 nM[13-20]Ach (10 uM)Xu et al. (2020)

Percentage inhibition: Nicotinic acetylcholine receptors

TargetOrganism% inhibitionConcentrationAgonistRef
α9α10H. sapiens76+/-2100 nMAch (6 uM)Wu X et al. (2017)

Synthetic variants
GeXIVA[C2A,C27A]TARSSGRYCRSPYDRRRRYCRRITDAAV
GeXIVA[C2S,C27S]TSRSSGRYCRSPYDRRRRYCRRITDASV
GeXIVA[C9A,C20A]TCRSSGRYARSPYDRRRRYARRITDACV
GeXIVA[C9S,C20S]TCRSSGRYSRSPYDRRRRYSRRITDACV
GeXIVA[insC_G, ribbon] cyclicTCRSSGRYCRSPYDRRRRYCRRITDACVG
GeXIVA[insC_GAAGG, ribbon] cyclicTCRSSGRYCRSPYDRRRRYCRRITDACVGAAGG
GeXIVA[insC_GAG, ribbon] cyclicTCRSSGRYCRSPYDRRRRYCRRITDACVGAG
GeXIVA[insC_GAGG, ribbon] cyclicTCRSSGRYCRSPYDRRRRYCRRITDACVGAGG
GeXIVA[insC_GG, ribbon] cyclicTCRSSGRYCRSPYDRRRRYCRRITDACVGG

References
Gao,B., Zhangsun,D., Wu,Y., Lin,B., Zhu,X. and Luo,S. (2013) Expression, renaturation and biological activity of recombinant conotoxin GeXIVAWT. Appl. Microbiol. Biotechnol. 97:1223-1230
Luo,S., Zhangsun,D., Harvey,P.J., Kaas,Q., Wu,Y., Zhu,X., Hu,Y., Li,X., Tsetlin,V.I., Christensen,S., Romero,H.K., McIntyre,M., Dowell,C., Baxter,J.C., Elmslie,K.S., Craik,D.J. and McIntosh,J.M. (2015) Cloning, synthesis, and characterization of αO-conotoxin GeXIVA, a potent α9α10 nicotinic acetylcholine receptor antagonist. Proc. Natl. Acad. Sci. U.S.A. 112-35
Wang, H., Li, X., Zhangsun, D., Yu, G., Su, R. and Luo, S. (2019) The α9α10 Nicotinic Acetylcholine Receptor Antagonist αO-Conotoxin GeXIVA[1,2] Alleviates and Reverses Chemotherapy-Induced Neuropathic Pain Marine drugs 17:265
Xu, P., Kaas, Q., Wu, Y., Zhu, X., Li, X., Harvey, P.J., Zhangsun, D., Craik, D.J. and Luo, S (2020) Structure and Activity Studies of Disulfide-Deficient Analogues of αO-Conotoxin GeXIVA Journal of Medicinal Chemistry
Yousuf A, Wu X, Bony AR, Sadeghi M, Huang YH, Craik DJ, Adams DJ (2021) αO-Conotoxin GeXIVA isomers modulate N-type calcium (CaV 2.2) channels and inwardly-rectifying potassium (GIRK) channels via GABAB receptor activation J Neurochem
Wu X, Huang YH, Kaas Q, Harvey PJ, Wang CK, Tae HS, Adams DJ, Craik DJ. (2017) Backbone cyclization of analgesic conotoxin GeXIVA facilitates direct folding of the ribbon isomer J Biol Chem 292:17101-17112

Internal links
Protein Precursor GeXIVA precursor (5224)
Nucleic acids
Structure

External links

Tools