GVIA (P01546) Protein Card

General Information

Name	GVIA
Alternative name(s)	G6a,SNX-124,Shaker peptide
Organism	Conus geographus (Geography cone)
Organism region	Indo-Pacific
Organism diet	piscivorous
Protein Type	Wild type
Protein precursor	GVIA precursor (820) GVIA precursor (5749)
Notes	Calcium Channel Blocker; Paralysis in lower vertebrates; shaking symptoms upon ic injection in mice. Kim et al. have performed an ala scan of GVIA (see references). GVIA was also shown by Horne et al. 1991,to bind to the α1 subunit of Torpedo nAChR.

Classification

Conopeptide class	conotoxin
Gene superfamily	O1 superfamily
Cysteine framework	VI/VII
Pharmacological family	omega conotoxin

Sequence

CKSOGSSCSOTSYNCCRSCNOYTKRCY(nh2)
Modified residues	position symbol name 4 O 4-Hydroxyproline 10 O 4-Hydroxyproline 21 O 4-Hydroxyproline 28 nh2 C-term amidation
Sequence evidence	protein level
Average Mass	3037.34
Monoisotopic Mass	3035.15
Isoelectric Point	12.58
Extinction Coefficient [280nm]	4470.00

Activity

IC50: Voltage-Gated Calcium Channels

Target	Organism	IC50		Competitor	Ref
Cav2.1	R. norvegicus	1.05uM		MVIIA	Lewis,R.J. et al. (2000)
Cav2.2	R. norvegicus	38pM		GVIA	Lewis,R.J. et al. (2000)
		2.02pM		1nM CnVIIA	Favreau,P. et al. (2001)
		3.7-4.3pM		1nM GVIA	Favreau,P. et al. (2001)
		28pM		GVIA	Mould,J. et al. (2004)
		134pM		MVIIA	Miljanich,G.P. et al. (1993)

Synthetic variants

GVIA [O10>K]	CKSOGSSCSKTSYNCCRSCNOYTKRCY(nh2)
GVIA[C8U,C19U]	CKSOGSSUSOTSYNCCRSUNOYTKRCY(nh2)

References

Olivera,B.M., McIntosh,J.M., Cruz,L.J., Luque,F.A. and Gray,W.R. (1984) Purification and sequence of a presynaptic peptide toxin from Conus geographus venom Biochemistry 23:5087-5090

Sato,K., Park,N.G., Kohno,T., Maeda,T., Kim,J.I., Kato,R. and Takahashi,M. (1993) Role of basic residues for the binding of omega-conotoxin GVIA to N-type calcium channels Biochem. Biophys. Res. Commun. 194:1292-1296

Kim,J.I., Takahashi,M., Ogura,A., Kohno,T., Kudo,Y. and Sato,K. (1994) Hydroxyl group of Tyr13 is essential for the activity of omega-conotoxin GVIA, a peptide toxin for N-type calcium channel J. Biol. Chem. 269:23876-23878

Lew,M.J., Flinn,J.P., Pallaghy,P.K., Murphy,R., Whorlow,S.L., Wright,C.E., Norton,R.S. and Angus,J.A. (1997) Structure-function relationships of omega-conotoxin GVIA. Synthesis, structure, calcium channel binding, and functional assay of alanine-substituted analogues J. Biol. Chem. 272:12014-12023

Davis,J.H., Bradley,E.K., Miljanich,G.P., Nadasdi,L., Ramachandran,J. and Basus,V.J. (1993) Solution structure of omega-conotoxin GVIA using 2-D NMR spectroscopy and relaxation matrix analysis Biochemistry 32:7396-7405

Pallaghy,P.K. and Norton,R.S. (1999) Refined solution structure of omega-conotoxin GVIA: implications for calcium channel binding J. Pept. Res. 53:343-351

Rivier,J., Galyean,R., Gray,W.R., Azimi-Zonooz,A., McIntosh,J.M., Cruz,L.J. and Olivera,B.M. (1987) Neuronal calcium channel inhibitors. Synthesis of omega-conotoxin GVIA and effects on 45Ca uptake by synaptosomes J. Biol. Chem. 262:1194-1198

Mould,J., Yasuda,T., Schroeder,C.I., Beedle,A.M., Doering,C.J., Zamponi,G.W., Adams,D.J. and Lewis,R.J. (2004) The alpha2delta auxiliary subunit reduces affinity of omega-conotoxins for recombinant N-type (Cav2.2) calcium channels J. Biol. Chem. 279:34705-34714

Kerr,L.M. and Yoshikami,D. (1984) A venom peptide with a novel presynaptic blocking action. Nature 308:282-284

Yoshikami,D. and Olivera,B.M. (1989) The inhibitory effects of omega-conotoxins on Ca channels and synapses. Ann. N. Y. Acad. Sci. 560:230-248

Lampe,R.A., Lo,M.M., Keith,R.A., Horn,M.B., McLane,M.W. and Spreen,R.C. (1993) Effects of site-specific acetylation on omega-conotoxin GVIA binding and function. Biochemistry 32:3255-3260

Flinn,J.P., Pallaghy,P.K., Lew,M.J., Murphy,R. and Norton,R.S. (1999) Role of disulfide bridges in the folding, structure and biological activity of omega-conotoxin GVIA. Biochim. Biophys. Acta 1434:177-190

Horne,W.A., Hawrot,E. and Tsien,R.W. (1991) omega-Conotoxin GVIA receptors of Discopyge electric organ. Characterization of omega-conotoxin binding to the nicotinic acetylcholine receptor. J. Biol. Chem. 266:13719-13725

Internal links

Protein Precursor	GVIA precursor (820) GVIA precursor (5749)
Nucleic acids
Structure	SOLUTION STRUCTURE OF OMEGA-CONOTOXIN GVIA USING 2-D NMR SPECTROSCOPY AND RELAXATION MATRIX ANALYSIS OMEGA-CONOTOXIN GVIA, A N-TYPE CALCIUM CHANNEL BLOCKER STRUCTURE OF THE CALCIUM CHANNEL BLOCKER OMEGA CONOTOXIN GVIA, NMR, 20 STRUCTURES

External links

Ncbi	2CCO_A, 1TTL_A, 1OMC_A

Tools

Please cite:
Kaas Q, Yu R, Jin AH, Dutertre S and Craik DJ. ConoServer: updated content, knowledge, and discovery tools in the conopeptide database. Nucleic Acids Research (2012) 40(Database issue):D325-30
Kaas Q, Westermann JC, Halai R, Wang CK and Craik DJ. ConoServer, a database for conopeptide sequences and structures. Bioinformatics (2008) 24(3):445-6

ConoServer is managed at the Institute of Molecular Bioscience IMB, Brisbane, Australia.

The database and computational tools found on this website may be used for academic research only, provided that it is referred to ConoServer, the database of conotoxins (http://www.conoserver.org) and the above reference is cited. For any other use please contact David Craik (d.craik@imb.uq.edu.au).

Contacts:
David Craik
Quentin Kaas

Last updated: Tuesday 19 January 2021