3-DIMENSIONAL STRUCTURE OF THE ALPHA-CONOTOXIN GI AT 1.2-ANGSTROM RESOLUTION

Predatory marine snails of the genus Conus paralyze their fish prey by injecting a potent toxin. The alpha-conotoxin GI is a 13-residue pept ide isolated from venom of Conus geographus. It functions by blocking the postsynaptic nicotinic acetylcholine receptor. After crystallizati on in deionized water, the three-dimensional structure of the GI neuro toxin was determined to 1.2 Angstrom resolution by X-ray crystallograp hy. This structure, which can be described as a trianglar slab, shows overall similarities to those derived by NMR, CD, and predictive metho ds. The principal framework of the molecule is provided by two disulfi de 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 hydro gen 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 (carb oxylate of Glu 1), and this is not implicated in receptor binding. Two positively charged regions (the cl-amino group of Glu 1 and the guani do group of Arg 9) are situated 15 Angstrom apart at the corners of th e triangular face of the molecule. phi,psi angles characteristic of a 3(10) helix were observed for residues 5-7. For residues 8-11, these a ngles were consistent with either a type I beta-turn or a distorted 3( 10) helix.