1MTQ

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

Summary for 1MTQ

• Entry DOI: 10.2210/pdb1mtq/pdb
• NMR Information: BMRB: 5585
• Descriptor: alpha-conotoxin GID (1 entity in total)
• Functional Keywords: alpha-helix, toxin
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 2193.45

Authors

Nicke, A.,Loughnan, M.L.,Millard, E.L.,Alewood, P.F.,Adams, D.J.,Daly, N.L.,Craik, D.J.,Lewis, R.J. (deposition date: 2002-09-22, release date: 2003-02-11, Last modification date: 2020-06-24)

Primary citation

Nicke, A.,Loughnan, M.L.,Millard, E.L.,Alewood, P.F.,Adams, D.J.,Daly, N.L.,Craik, D.J.,Lewis, R.J.
Isolation, Structure, and Activity of GID, a Novel alpha 4/7-Conotoxin with an Extended N-terminal Sequence
J.BIOL.CHEM., 278:3137-3144, 2003

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.

PubMed: 12419800
DOI: 10.1074/jbc.M210280200

Experimental method

SOLUTION NMR