title: Concentration-dependent realignment of the antimicrobial peptide PGLa in lipid membranes observed by solid-state 19F-NMR.
abstract: The membrane-disruptive antimicrobial peptide PGLa is found to change its orientation in a dimyristoyl-phosphatidylcholine bilayer when its concentration is increased to biologically active levels. The alignment of the alpha-helix was determined by highly sensitive solid-state NMR measurements of (19)F dipolar couplings on CF(3)-labeled side chains, and supported by a nonperturbing (15)N label. At a low peptide/lipid ratio of 1:200 the amphiphilic peptide resides on the membrane surface in the so-called S-state, as expected. However, at high peptide concentration (>/=1:50 molar ratio) the helix axis changes its tilt angle from approximately 90 degrees to approximately 120 degrees , with the C-terminus pointing toward the bilayer interior. This tilted "T-state" represents a novel feature of antimicrobial peptides, which is distinct from a membrane-inserted I-state. At intermediate concentration, PGLa is in exchange between the S- and T-state in the timescale of the NMR experiment. In both states the peptide molecules undergo fast rotation around the membrane normal in liquid crystalline bilayers; hence, large peptide aggregates do not form. Very likely the obliquely tilted T-state represents an antiparallel dimer of PGLa that is formed in the membrane at increasing concentration.
authors.affiliation: Institute of Biochemistry and Biophysics, University of Jena, Jena, Germany.
authors.forename: Ralf W
authors.initials: RW
authors.lastname: Glaser
authors.forename: Carsten
authors.initials: C
authors.lastname: Sachse
authors.forename: Ulrich H N
authors.initials: UH
authors.lastname: Dürr
authors.forename: Parvesh
authors.initials: P
authors.lastname: Wadhwani
authors.forename: Sergii
authors.initials: S
authors.lastname: Afonin
authors.forename: Erik
authors.initials: E
authors.lastname: Strandberg
authors.forename: Anne S
authors.initials: AS
authors.lastname: Ulrich
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D001703:Biophysics / Q000379:methods*; D002152:Calorimetry, Differential Scanning; D002244:Carbon / Q000737:chemistry; D002462:Cell Membrane / Q000378:metabolism; D003198:Computer Simulation; D019281:Dimerization; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D004161:Diphenylhexatriene / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000494:pharmacology; D006838:Hydrocarbons / Q000737:chemistry; D008051:Lipid Bilayers; D008055:Lipids / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary; D012984:Software; D055672:Static Electricity; D013696:Temperature; D013997:Time Factors
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D005456:Fluorescent Dyes; D006838:Hydrocarbons; D008051:Lipid Bilayers; D008055:Lipids; D010455:Peptides; C045866:peptide-Gly-Leu-amide; D004161:Diphenylhexatriene; D015060:1,2-Dipalmitoylphosphatidylcholine; D002244:Carbon; D004134:Dimyristoylphosphatidylcholine