Solution structure of α-conotoxin MI determined by -NMR spectroscopy and molecular dynamics simulation with the explicit solvent water

The present study provides a molecular basis for the α-conotoxin–receptor interaction and indicates the presence of a 310 helix and a type I β-turn for residues Pro6–Cys8 and Gly9–Try12, respectively.

Abstract

The conformation of alpha-conotoxin MI, a potent antagonist of the nicotinic acetylcholine receptor, has been investigated in aqueous solution. Two-dimensional NMR experiments and simulated annealing calculations provide the overall topology of alpha-conotoxin MI; then molecular dynamics simulation with the explicit solvent water was followed in order to obtain a more reliable solution structure. The resulting conformation indicates the presence of a 3(10) helix and a type I beta-turn for residues Pro6-Cys8 and Gly9-Try12, respectively, and shows a significant structural similarity to that of alpha-conotoxin GI, which has biological activity similar to that of MI. The present study provides a molecular basis for the alpha-conotoxin-receptor interaction.