Asymmetrical ion-channel model inferred from two-dimensional crystallization of a peptide antibiotic

The structural organization of ion channels formed in lipid membranes by am phiphilic alpha-helical peptides is deduced by applying direct structural m ethods to different lipid/alamethicin systems. Alamethicin represents a hyd rophobic cy-helical peptide antibiotic forming voltage-gated ion channels i n lipid membranes. Here the first direct evidence for the existence of larg e-scale two-dimensional crystalline domains of alamethicin helices, oriente d parallel to the air/water interface, is presented using synchrotron x-ray diffraction, fluorescence microscopy, and surface pressure/area isotherms. Proofs are obtained that the antibiotic peptide injected into the aqueous phase under phospholipid monolayers penetrates these monolayers, phase sepa rates, and forms domains within the lipid environment, keeping the same, pa rallel orientation of the alpha-helices with respect to the phospholipid/wa ter interface. A new asymmetrical, "lipid-covered ring" model of the voltag e-gated ion channel of alamethicin is inferred from the structural results presented, and the mechanism of ion-channel formation is discussed.