NMR spatial structure of alpha-conotoxin ImI reveals a common scaffold in snail and snake toxins recognizing neuronal nicotinic acetylcholine receptors

A 600 MHz NMR study of alpha-conotoxin ImI from Conus imperialis, targeting the alpha 7 neuronal nicotinic acetylcholine receptor (nAChR), is presente d. ImI backbone spatial structure is well defined basing on the NOEs, spin- spin coupling constants, and amide protons hydrogen-deuterium exchange data : rmsd of the backbone atom coordinates at the 2-12 region is 0.28 Angstrom in the 20 best structures, The structure is described as a type I beta-tur n (positions 2-5) followed by a distorted helix (positions 5-11). Similar s tructural psattern can be found in all neuronal-specific alpha-conotoxins. Highly mobile side chains of the Asp-5, Arg-7 and Trp-10 residues form a si ngle site for ImI binding to the alpha 7 receptor. When depicted with oppos ite directions of the polypeptide chains, the ImI helix and the tip of the central loop of long chain snake neurotoxins demonstrate a common scaffold and similar positioning of the functional side chains, both of these struct ural elements appearing essential for binding to the neuronal nAChRs. (C) 1 999 Federation of European Biochemical Societies.