title: Effects of arginine density on the membrane-bound structure of a cationic antimicrobial peptide from solid-state NMR.
abstract: Solid-state NMR spectroscopy is used to determine the membrane-bound topological structure of a cationic beta-hairpin antimicrobial peptide in which the number of Arg residues has been halved. The parent peptide, PG-1, was previously found to form transmembrane beta-barrels in anionic membranes where the Arg residues complex with the lipid phosphate groups to cause toroidal pore defects in the membrane. In comparison, the charge-attenuated and less active mutant studied here forms beta-sheets that lie on the surface of the zwitterionic membrane and only partially insert into the anionic membrane. The mutant also exhibits much looser contact with the lipid headgroups. These results indicate that transmembrane insertion and tight Arg-phosphate association are two important elements for strong antimicrobial activities of this class of peptides. Comparison with other beta-hairpin antimicrobial peptides studied so far further suggests a relative potency scale for the various mechanisms of action for the beta-sheet family of antimicrobial peptides. The transmembrane insertion-toroidal pore mechanism is the most potent in disrupting the lipid bilayer, followed by the large-amplitude in-plane motional mechanism. The carpet model, where peptides aggregate on the membrane surface to cause lateral expansion and eventual micellization of the membrane, is a weaker mechanism of action.
authors.affiliation: Department of Chemistry, Iowa State University, Ames, IA 50011, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Tang
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Waring
authors.forename: Mei
authors.initials: M
authors.lastname: Hong
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D001120:Arginine / Q000737:chemistry; D004058:Diffusion; D008051:Lipid Bilayers / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data
chemical_list: D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D001120:Arginine