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Protein

Alpha-conotoxin GIA

Gene
N/A
Organism
Conus geographus (Geography cone) (Nubecula geographus)
Status
Reviewed-Annotation score: Annotation score: 3 out of 5-Experimental evidence at protein leveli

Functioni

Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. The higher affinity site for alpha-conotoxin GI is the alpha/delta site on mouse muscle-derived BC3H-1 receptor, and the other site (alpha/gamma site) on nicotinic receptors from Torpedo californica electric organ.

Keywords - Molecular functioni

Acetylcholine receptor inhibiting toxin, Ion channel impairing toxin, Neurotoxin, Postsynaptic neurotoxin, Toxin

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-conotoxin GIA
Cleaved into the following chain:
Alternative name(s):
G1
OrganismiConus geographus (Geography cone) (Nubecula geographus)
Taxonomic identifieri6491 [NCBI]
Taxonomic lineageiEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaHypsogastropodaNeogastropodaConoideaConidaeConus

Organism-specific databases

ConoServeri74. GI.
22. GIA.

Subcellular locationi

  1. Secreted 1 Publication

GO - Cellular componenti

  1. other organism postsynaptic membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi9 – 91R → A: Reduction in affinity for both alpha/delta and alpha/gamma sites on BC3H-1 receptors and loss of affinity for both alpha/delta and alpha/gamma sites on Torpedo receptors (in GI). 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Peptidei1 – 1515Alpha-conotoxin GIAPRO_0000034873Add
BLAST
Peptidei1 – 1313Alpha-conotoxin GIPRO_0000034874Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi2 ↔ 79 Publications
Disulfide bondi3 ↔ 139 Publications
Modified residuei13 – 131Cysteine amide; in alpha-conotoxin GI
Modified residuei15 – 151Lysine amide; in form alpha-conotoxin GIA

Post-translational modificationi

Not hydroxylated; hydroxylation, on a synthetic hydroxylated GI, improves its folding but impairs its activity against target receptors.

Keywords - PTMi

Amidation, Disulfide bond

Expressioni

Tissue specificityi

Expressed by the venom duct.Curated

Structurei

Secondary structure

1
15
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi5 – 106Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1NOTX-ray1.20A1-13[»]
1QS3NMR-A2-12[»]
1XGANMR-A1-13[»]
1XGBNMR-A1-13[»]
1XGCNMR-A1-13[»]
2FR9NMR-A1-11[»]
2FRBNMR-A1-13[»]
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01519.

Family & Domainsi

Domaini

The cysteine framework is I (CC-C-C). Alpha3/5 pattern.Curated

Sequence similaritiesi

Belongs to the conotoxin A superfamily.Curated

Family and domain databases

InterProiIPR018072. Conotoxin_a-typ_CS.
[Graphical view]
PROSITEiPS60014. ALPHA_CONOTOXIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Length:15
Mass (Da):1,628
Last modified:July 21, 1986 - v1
Checksum:i2AE73EE90F8C2E19
GO

Sequence databases

PIRiA01782. NTKNAG.

Cross-referencesi

Sequence databases

PIRiA01782. NTKNAG.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1NOTX-ray1.20A1-13[»]
1QS3NMR-A2-12[»]
1XGANMR-A1-13[»]
1XGBNMR-A1-13[»]
1XGCNMR-A1-13[»]
2FR9NMR-A1-11[»]
2FRBNMR-A1-13[»]
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

ConoServeri74. GI.
22. GIA.

Miscellaneous databases

EvolutionaryTraceiP01519.

Family and domain databases

InterProiIPR018072. Conotoxin_a-typ_CS.
[Graphical view]
PROSITEiPS60014. ALPHA_CONOTOXIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Peptide toxins from Conus geographus venom."
    Gray W.R., Luque A., Olivera B.M., Barrett J., Cruz L.J.
    J. Biol. Chem. 256:4734-4740(1981) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE, SUBCELLULAR LOCATION.
  2. "Primary and secondary structure of conotoxin GI, a neurotoxic tridecapeptide from a marine snail."
    Nishiuchi Y., Sakakibara S.
    FEBS Lett. 148:260-262(1982) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISULFIDE BONDS IN GI, SYNTHESIS OF GI.
  3. "Conotoxin GI: disulfide bridges, synthesis, and preparation of iodinated derivatives."
    Gray W.R., Luque F.A., Galyean R., Atherton E., Sheppard R.C., Stone B.L., Reyes A., Alford J., McIntosh M., Olivera B.M., Cruz L.J., Rivier J.
    Biochemistry 23:2796-2802(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISULFIDE BONDS IN GI, SYNTHESIS OF GI.
  4. "The alpha-conotoxins GI and MI distinguish between the nicotinic acetylcholine receptor agonist sites while SI does not."
    Hann R.M., Pagan O.R., Eterovic V.A.
    Biochemistry 33:14058-14063(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: COMPARISON WITH ALPHA-CONOTOXIN SI AND ALPHA-CONOTOXIN MI.
  5. "Alpha-conotoxins selectively inhibit one of the two acetylcholine binding sites of nicotinic receptors."
    Groebe D.R., Dumm J.M., Levitan E.S., Abramson S.N.
    Mol. Pharmacol. 48:105-111(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHARMACOLOGICAL CHARACTERIZATION ON MOUSE MUSCLE-DERIVED BC3H-1 CELLS AND TORPEDO ELECTRIC ORGAN.
  6. "Determinants involved in the affinity of alpha-conotoxins GI and SI for the muscle subtype of nicotinic acetylcholine receptors."
    Groebe D.R., Gray W.R., Abramson S.N.
    Biochemistry 36:6469-6474(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF ARG-9.
  7. "Role of hydroxyprolines in the in vitro oxidative folding and biological activity of conotoxins."
    Lopez-Vera E., Walewska A., Skalicky J.J., Olivera B.M., Bulaj G.
    Biochemistry 47:1741-1751(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: SYNTHESIS, ROLE OF HYDROXYLATION.
  8. "Modulation of conotoxin structure and function is achieved through a multienzyme complex in the venom glands of cone snails."
    Safavi-Hemami H., Gorasia D.G., Steiner A.M., Williamson N.A., Karas J.A., Gajewiak J., Olivera B.M., Bulaj G., Purcell A.W.
    J. Biol. Chem. 287:34288-34303(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISULFIDE BONDS, FOLDING.
    Tissue: Venom.
  9. "Three-dimensional structure of the alpha-conotoxin GI at 1.2-A resolution."
    Guddat L.W., Martin J.A., Shan L., Edmundson A.B., Gray W.R.
    Biochemistry 35:11329-11335(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF GI, DISULFIDE BONDS.
  10. "Solution conformation of conotoxin GI determined by 1H nuclear magnetic resonance spectroscopy and distance geometry calculations."
    Kobayashi Y., Ohkubo T., Kyogoku Y., Nishiuchi Y., Sakakibara S., Braun W., Go N.
    Biochemistry 28:4853-4860(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF GI, DISULFIDE BONDS.
  11. "Solution structures of alpha-conotoxin G1 determined by two-dimensional NMR spectroscopy."
    Pardi A., Galdes A., Florance J., Maniconte D.
    Biochemistry 28:5494-5501(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF GI, DISULFIDE BONDS.
  12. Cited for: STRUCTURE BY NMR OF GI, DISULFIDE BONDS.
  13. "Structure determination of the three disulfide bond isomers of alpha-conotoxin GI: a model for the role of disulfide bonds in structural stability."
    Gehrmann J., Alewood P.F., Craik D.J.
    J. Mol. Biol. 278:401-415(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF GI, DISULFIDE BONDS.
  14. "NMR solution conformation of an antitoxic analogue of alpha-conotoxin GI: identification of a common nicotinic acetylcholine receptor alpha(1)-subunit binding surface for small ligands and alpha-conotoxins."
    Mok K.H., Han K.H.
    Biochemistry 38:11895-11904(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF AN ANTITOXIC ANALOG OF GI, DISULFIDE BONDS.

Entry informationi

Entry nameiCA1A_CONGE
AccessioniPrimary (citable) accession number: P01519
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: February 4, 2015
This is version 95 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Miscellaneousi

Miscellaneous

This toxin is a substrate for a cone snail multienzyme complex that regulates its folding and assembly. This complex is composed of protein-disulfide isomerase (PDI), peptidyl-prolyl cis-trans isomerase (PPI) and immunoglobulin-binding protein (BiP). PDI catalyzes the oxidation and reduction of disulfide bonds. Oxidative folding rates are further increased in the presence of PPI with the maximum effect observed in the presence of both enzymes. In contrast, BiP is only observed to assist folding in the presence of microsomes, suggesting that additional cofactors are involved. This toxin has been only observed in the globular form (disulfide pattern C1-C3 and C2-C4).1 Publication

Keywords - Technical termi

3D-structure, Direct protein sequencing

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.