A voltage-gated ion channel model inferred from the crystal structure of alamethicin at 1.5-Å resolution

Abstract

The crystal structure of alamethicin in nonaqueous solvent was determined and refined at 1.5-.ANG. resolution. The molecular conformation of the 3 crystallographically independent molecules is largely .alpha.-helical with a bend in the helix axis at an internal proline residue. The helix structure is highly amphipathic as most of the solvent-accessible polar atoms lie on a narrow strip of surface parallel to the helix axis. Molecular models for the voltage-gated ion channel, with n-fold symmetry and based on the molecular conformations observed in the crystal, are characterized by strong surface complementarity, a hydrophilic interior and a hydrophobic exterior. The channel structures are stabilized by a hydrated annulus of H-bonded glutamine residues which produce the greatest restriction in the channel diameter.