title: Interaction of the peptide antibiotic alamethicin with bilayer- and non-bilayer-forming lipids: influence of increasing alamethicin concentration on the lipids supramolecular structures.
abstract: Incorporation of the helical antimicrobial peptide alamethicin from aqueous phase into hydrated phases of dioleoylphosphatidylethanolamine (DOPE) and dioleoylphosphatidylcholine (DOPC) was investigated within a range of peptide concentrations and temperatures by time-resolved synchrotron X-ray diffraction. It was found that alamethicin influences the organizations of the non-bilayer-forming (DOPE) and the bilayer-forming (DOPC) lipids in different ways. In DOPC, only the bilayer thickness was affected, while in DOPE new phases were induced. At low peptide concentrations (<1.10(-4) M), an inverted hexagonal (H(II)) phase was observed as with DOPE dispersions in pure buffer solution. A coexistence of two cubic structures was found at the critical peptide concentration for induction of new lipid/peptide phases. The first one Q224 (space group Pn3m) was identified within the entire temperature region studied (from 1 to 45 degrees C) and was found in coexistence with H(II)-phase domains. The second lipid/peptide cubic structure was present only at temperatures below 16 degrees C and its X-ray reflections were better fitted by a Q212 (P4(3)32) space group, rather than by the expected Q229 (Im3m) space group. At alamethicin concentrations of 1 mM and higher, a nonlamellar phase transition from a Q224 cubic phase into an H(II) phase was observed. Within the investigated range of peptide concentrations, lamellar structures of two different bilayer periods were established with the bilayer-forming lipid DOPC. They correspond to lipid domains of associated and nonassociated helical peptide. The obtained X-ray results suggest that the amphiphilic alamethicin molecules adsorb from the aqueous phase at the lipid head group/water interface of the DOPE and DOPC membranes. At sufficiently high (>1.10(-4) M) solution concentrations, the peptide is probably accommodated in the head group region of the lipids thus inducing structural features of mixed lipid/peptide phases.
authors.affiliation: College of Sciences Leonardo da Vinci, Sofia, Bulgaria. a-angelova@usa.net
authors.forename: A
authors.initials: A
authors.lastname: Angelova
authors.forename: R
authors.initials: R
authors.lastname: Ionov
authors.forename: M H
authors.initials: MH
authors.lastname: Koch
authors.forename: G
authors.initials: G
authors.lastname: Rapp
mesh_terms: D000408:Alamethicin / Q000737:chemistry*; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D011487:Protein Conformation; D013816:Thermodynamics; D014867:Water; D014961:X-Ray Diffraction
chemical_list: D000900:Anti-Bacterial Agents; D008051:Lipid Bilayers; D046911:Macromolecular Substances; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D014867:Water; D000408:Alamethicin; C020888:1,2-dielaidoylphosphatidylethanolamine; C017251:1,2-oleoylphosphatidylcholine