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Solution conformation of α-conotoxin GIC, a novel potent antagonist of α3β2 nicotinic acetylcholine receptors

被引：26
作者：
Chi, SW
Kim, DH
Olivera, BM
Mcintosh, JM
Han, KH
机构：
[1] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA
[2] Korea Res Inst Biosci & Biotechnol, Div Drug Discovery, Lab Prot Anal & Design, Taejon, South Korea
[3] Univ Utah, Dept Psychiat, Salt Lake City, UT 84112 USA
来源：
BIOCHEMICAL JOURNAL | 2004年 / 380卷
关键词：
alpha-conotoxin; Conus geographus (cone snail); nicotinic acetylcholine receptor (nAChR); NMR; solution structure; venom;
D O I：
10.1042/BJ20031792
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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 Angstrom and 0.96 Angstrom 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.
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收藏
页码：347 / 352
页数：6
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