title: Membrane thinning effect of the beta-sheet antimicrobial protegrin.
abstract: Lipid bilayers containing the antimicrobial peptide protegrin-1 (PG-1) were studied by lamellar X-ray diffraction. Previously, we have shown that the peptide exists in two distinct states when associated with lipid bilayers depending on the peptide concentration [Heller, W. T., Waring, A. J., Lehrer, R. I., and Huang, H. W. (1998) Biochemistry 37, 17331-17338]. For concentrations below a lipid-dependent threshold, PG-1 exhibits a unique oriented circular dichroism spectrum called the S state. X-ray experiments show that in this state PG-1 decreases the thickness of the lipid bilayer in proportion to the peptide concentration, similar to alamethicin's membrane thinning effect. This indicates that the S state is adsorbed in the headgroup region of the lipid bilayer, where the peptide is in an inactive state. For PG-1 above the threshold concentration, X-ray diffraction shows that the interaction between the peptide and the bilayer changes significantly. These results suggest that PG-1 has the same concentration-gated mechanism of action as alamethicin.
authors.affiliation: Department of Physics, Rice University, Houston, Texas 77251, USA.
authors.forename: W T
authors.initials: WT
authors.lastname: Heller
authors.forename: A J
authors.initials: AJ
authors.lastname: Waring
authors.forename: R I
authors.initials: RI
authors.lastname: Lehrer
authors.forename: T A
authors.initials: TA
authors.lastname: Harroun
authors.forename: T M
authors.initials: TM
authors.lastname: Weiss
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.forename: H W
authors.initials: HW
authors.lastname: Huang
mesh_terms: D000408:Alamethicin / Q000737:chemistry; D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D010455:Peptides; D010713:Phosphatidylcholines; D011506:Proteins; C094880:protegrin-1; D000408:Alamethicin; C021016:1,2-diphytanoylphosphatidylcholine