1MTQ

THREE-DIMENSIONAL SOLUTION STRUCTURE OF ALPHA-CONOTOXIN GID BY NMR SPECTROSCOPY


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 50 
  • Conformers Submitted: 20 
  • Selection Criteria: all calculated structures submitted, structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 2.0 of the entry. See complete history


Literature

Isolation, Structure, and Activity of GID, a Novel alpha 4/7-Conotoxin with an Extended N-terminal Sequence

Nicke, A.Loughnan, M.L.Millard, E.L.Alewood, P.F.Adams, D.J.Daly, N.L.Craik, D.J.Lewis, R.J.

(2003) J Biol Chem 278: 3137-3144

  • DOI: https://doi.org/10.1074/jbc.M210280200
  • Primary Citation of Related Structures:  
    1MTQ

  • PubMed Abstract: 

    Using assay-directed fractionation of Conus geographus crude venom, we isolated alpha-conotoxin GID, which acts selectively at neuronal nicotinic acetylcholine receptors (nAChRs). Unlike other neuronally selective alpha-conotoxins, alpha-GID has a four amino acid N-terminal tail, gamma-carboxyglutamate (Gla), and hydroxyproline (O) residues, and lacks an amidated C terminus. GID inhibits alpha 7 and alpha 3 beta 2 nAChRs with IC(50) values of 5 and 3 nm, respectively and is at least 1000-fold less potent at the alpha 1 beta 1 gamma delta, alpha 3 beta 4, and alpha 4 beta 4 combinations. GID also potently inhibits the alpha 4 beta 2 subtype (IC(50) of 150 nm). Deletion of the N-terminal sequence (GID Delta 1-4) significantly decreased activity at the alpha 4 beta 2 nAChR but hardly affected potency at alpha 3 beta 2 and alpha 7 nAChRs, despite enhancing the off-rates at these receptors. In contrast, Arg(12) contributed to alpha 4 beta 2 and alpha 7 activity but not to alpha 3 beta 2 activity. The three-dimensional structure of GID is well defined over residues 4-19 with a similar motif to other alpha-conotoxins. However, despite its influence on activity, the tail appears to be disordered in solution. Comparison of GID with other alpha 4/7-conotoxins which possess an NN(P/O) motif in loop II, revealed a correlation between increasing length of the aliphatic side-chain in position 10 (equivalent to 13 in GID) and greater alpha 7 versus alpha 3 beta 2 selectivity.


  • Organizational Affiliation

    Institute for Molecular Bioscience and School of Biomedical Sciences, University of Queensland, Brisbane, Queensland 4072, Australia.


Macromolecules

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
alpha-conotoxin GID19synthetic constructMutation(s): 0 
Membrane Entity: Yes 
UniProt
Find proteins for P60274 (Conus geographus)
Explore P60274 
Go to UniProtKB:  P60274
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP60274
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  2 Unique
IDChains TypeFormula2D DiagramParent
CGU
Query on CGU
A
L-PEPTIDE LINKINGC6 H9 N O6GLU
HYP
Query on HYP
A
L-PEPTIDE LINKINGC5 H9 N O3PRO
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 50 
  • Conformers Submitted: 20 
  • Selection Criteria: all calculated structures submitted, structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-02-11
    Type: Initial release
  • Version 1.1: 2008-04-28
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 2.0: 2020-06-24
    Changes: Atomic model, Data collection, Database references, Derived calculations, Source and taxonomy