title: Immobilization and aggregation of the antimicrobial peptide protegrin-1 in lipid bilayers investigated by solid-state NMR.
abstract: The dynamics and aggregation of a beta-sheet antimicrobial peptide, protegrin-1 (PG-1), are investigated using solid-state NMR spectroscopy. Chemical shift anisotropies of F12 and V16 carbonyl carbons are uniaxially averaged in 1,2-dilauryl-sn-glycero-3-phosphatidylcholine (DLPC) bilayers but approach rigid-limit values in the thicker 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphatidylcholine (POPC) bilayers. The Calpha-Halpha dipolar coupling of L5 is scaled by a factor of 0.16 in DLPC bilayers but has a near-unity order parameter of 0.96 in POPC bilayers. The larger couplings of PG-1 in POPC bilayers indicate immobilization of the peptide, suggesting that PG-1 forms oligomeric aggregates at the biologically relevant bilayer thickness. Exchange NMR experiments on F12 (13)CO-labeled PG-1 show that the peptide undergoes slow reorientation with a correlation time of 0.7 +/- 0.2 s in POPC bilayers. This long correlation time suggests that in addition to aggregation, geometric constraints in the membrane may also contribute to PG-1 immobilization. The PG-1 aggregates contact both the surface and the hydrophobic center of the POPC bilayer, as determined by (1)H spin-diffusion measurements. Thus, solid-state NMR provides a wide range of information about the molecular details of membrane peptide immobilization and aggregation in lipid bilayers.
authors: Department of Chemistry, Iowa State University, Ames, Iowa 50011, USA.
authors: Jarrod J
authors: JJ
authors: Buffy
authors: Alan J
authors: AJ
authors: Waring
authors: Robert I
authors: RI
authors: Lehrer
authors: Mei
authors: M
authors: Hong
mesh_terms: D016880:Anisotropy; D023181:Antimicrobial Cationic Peptides; D004058:Diffusion; D008051:Lipid Bilayers / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D010767:Phosphorylcholine / Q000737:chemistry; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*
chemical_list: D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D011506:Proteins; C094880:protegrin-1; D010767:Phosphorylcholine