Three-dimensional structure of the a-conotoxin GI at 1.2 Å resolution

Abstract

Predatory marine snails of the genus Conus paralyze their fish prey by injecting a potent toxin. The α-conotoxin GI is a 13-residue peptide isolated from venom of Conus geographus. It functions by blocking the postsynaptic nicotinic acetylcholine receptor. After crystallization in deionized water, the three-dimensional structure of the GI neurotoxin was determined to 1.2 Å resolution by X-ray crystallography. This structure, which can be described as a trianglar slab, shows overall similarities to those derived by NMR, CD, and predictive methods. The principal framework of the molecule is provided by two disulfide bonds, one linking Cys 2 and Cys 7 and the other Cys 3 and Cys 13. Opposite ends of the sequence are drawn together even further by hydrogen bonds between Glu 1 and Cys 13 and between Cys 2 and Ser 12. Since the C-terminus is amidated, only one negative charge is present (carboxylate of Glu 1), and this is not implicated in receptor binding. Two positively charged regions (the α-amino group of Glu 1 and the guanido group of Arg 9) are situated 15 Å apart at the corners of the triangular face of the molecule. φ,ψ angles characteristic of a 310 helix were observed for residues 5−7. For residues 8−11, these angles were consistent with either a type I β-turn or a distorted 310 helix.