Three-dimensional solution structure of α-conotoxin MII, an α3β2 neuronal nicotinic acetylcholine receptor-targeted ligand

被引:53
作者
Shon, KJ [1 ]
Koerber, SC
Rivier, JE
Olivera, BM
McIntosh, JM
机构
[1] Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USA
[2] Salk Inst Biol Studies, Clayton Fdn, Labs Peptide Biol, La Jolla, CA 92037 USA
[3] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA
[4] Univ Utah, Dept Psychiat, Salt Lake City, UT 84112 USA
关键词
D O I
10.1021/bi971443r
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 MII, isolated from Conus magus, is a potent peptidic toxin which specifically targets the mammalian neuronal nicotinic acetylcholine receptor, alpha(3) beta(2) subtype. The three-dimensional structure of alpha-conotoxin MII in aqueous solution has been determined by two-dimensional H-1 NMR spectroscopy. NOE-derived distances, refined by an iterative relaxation matrix approach, as well as dihedral and chirality restraints were used in high-temperature biphasic simulated annealing calculations. Fourteen minimum energy structures out of 50 subjected to the SA simulations were chosen for evaluation; these 14 structures have a final RMS deviation of 0.76 +/- 0.31 and 1.35 +/- 0.34 Angstrom for the backbone and heavy atoms, respectively. The overall structure is unusually well-defined due to a large helical component around the two disulfide bridges. The principal backbone folding motif may be common to a subclass of alpha-conotoxins. There are two distinct surfaces on the molecule almost at right angles to one another. One entirely consists of the hydrophobic residues Gly(1), Cys(2), Cys(3), Leu(15), and Cys(16). The second comprises the hydrophilic residues Glu(11), His(12), Ser(13), and Asn(14). These surfaces on the ligand could be essential for the subtype-specific recognition of the receptor.
引用
收藏
页码:15693 / 15700
页数:8
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