Solution conformation of alpha-conotoxin GIC, a novel potent antagonist of alpha3beta2 nicotinic acetylcholine receptors.
Alpha-conotoxin GIC is a 16-residue peptide isolated from the venom of the cone snail Conus geographus. Alpha-conotoxin GIC potently blocks the alpha3beta2 subtype of human nicotinic acetylcholine receptor, showing a high selectivity for neuronal versus muscle subtype [McIntosh, Dowell, Watkins, Garrett, Yoshikami, and Olivera (2002) J. Biol. Chem. 277, 33610-33615]. We have now determined the three-dimensional solution structure of alpha-conotoxin GIC by NMR spectroscopy. The structure of alpha-conotoxin GIC is well defined with backbone and heavy atom root mean square deviations (residues 2-16) of 0.53 A and 0.96 A respectively. Structure and surface comparison of alpha-conotoxin GIC with the other alpha4/7 subfamily conotoxins reveals unique structural aspects of alpha-conotoxin GIC. In particular, the structural comparison between alpha-conotoxins GIC and MII indicates molecular features that may confer their similar receptor specificity profile, as well as those that provide the unique binding characteristics of alpha-conotoxin GIC.
Laboratory of Protein Analysis and Design, Division of Drug Discovery, Korea Research Institute of Bioscience and Biotechnology, Yusong P.O. Box 115, Daejon, Korea.
Seung-Wook
SW
Chi
Do-Hyoung
DH
Kim
Baldomero M
BM
Olivera
J Michael
JM
McIntosh
Kyou-Hoon
KH
Han
D000595:Amino Acid Sequence; D000818:Animals; D020916:Conotoxins / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008961:Models, Structural; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000737:chemistry / Q000494:pharmacology; D009124:Muscle Proteins / Q000378:metabolism; D009132:Muscles / Q000737:chemistry; D009474:Neurons / Q000737:chemistry; D018733:Nicotinic Antagonists / Q000737:chemistry / Q000494:pharmacology; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012996:Solutions
D020916:Conotoxins; D008978:Mollusk Venoms; D009124:Muscle Proteins; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D012996:Solutions; C419362:nicotinic receptor alpha3beta2