title: Peptide-induced formation of cholesterol-rich domains.
abstract: The peptide N-acetyl-LWYIK-amide causes the reorganization of bilayers of phosphatidylcholine and cholesterol to produce domains enriched in cholesterol. At a cholesterol mol fraction of 0.5, addition of N-acetyl-LWYIK-amide results in the formation of cholesterol crystallites. Addition of this peptide to mixtures of 1-stearoyl-2-oleoylphosphatidylcholine with lower mol fractions of cholesterol results in an increase in the enthalpy of the chain melting transition of the phospholipid, indicating the depletion of cholesterol from a domain in the membrane. The peptide binds to membranes both with and without cholesterol. However, (1)H magic-angle spinning (MAS) nuclear Overhauser effect spectroscopy (NOESY) indicates that in the presence of cholesterol the peptide has greater penetration into the bilayer. (13)C MAS NMR indicates that the peptide has stronger interactions with the A ring of cholesterol than it does with the interior of the bilayer. These results are in contrast with those of another peptide, N-acetyl-KYWFYR-amide, which does not promote the formation of cholesterol crystallites and does not show preferential interaction with cholesterol by NMR. Therefore, cholesterol can promote the insertion of N-acetyl-LWYIK-amide into a membrane and this peptide will sequester cholesterol into domains. These properties help to explain the observation that this sequence is found to be important in causing the fusion protein of human immunodeficiency virus (HIV) to sequester into raft domains in biological membranes.
authors.affiliation: Department of Biochemistry, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Epand
authors.forename: Brian G
authors.initials: BG
authors.lastname: Sayer
authors.forename: Raquel F
authors.initials: RF
authors.lastname: Epand
mesh_terms: D002152:Calorimetry, Differential Scanning; D002240:Carbohydrate Sequence; D002247:Carbon Isotopes; D002784:Cholesterol / Q000737:chemistry* / Q000378:metabolism*; D003460:Crystallization; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D017434:Protein Structure, Tertiary; D011522:Protons; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics; D014364:Tryptophan
chemical_list: D002247:Carbon Isotopes; D008051:Lipid Bilayers; D008081:Liposomes; D009842:Oligopeptides; D010713:Phosphatidylcholines; D011522:Protons; C027891:1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine; D014364:Tryptophan; D002784:Cholesterol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine