title: Lipid-protein interactions in the membrane: studies with model peptides.
abstract: We have used fluorescence quenching of tryptophan-containing trans-membrane peptides by bromine-containing phospholipids to study the specificity of peptide-lipid interactions. We have synthesized peptides Ac-K2GLm WLnK2A-amide where m = 7 and n = 9 (L16) and m = 10 and n = 12 (L22). Binding constants of L22 for dioleoylphosphatidylserine [di(C18 : 1)PS] or dioleoylphosphatidic acid [di(C18 : 1)PA] relative to dieoleoylphosphatidylcholine [di(C18 : 1)PC] were close to 1. However, for L16, whilst the bulk of the di(C18 : 1)PA molecules bound with a binding constant relative to di(C18 : 1)PC close to 1, a small number of di(C18 : 1)PA molecules bound much more strongly. Assuming just one high affinity binding site on L16 for anionic lipid, the affinity of the site for di(C18 : 1)PS was calculated to be ca. 8 times that for di (C18 : 1)PC. The relative binding constant was little affected by ionic strength and close contact between the anionic headgroup of di(C18 : 1)PS and a lysine residue on the peptide was suggested. The relative binding constant for di(C18 : 1)PS at this high affinity site was less than for di(C18 : 1)PA. Cholesterol interacts with L22 with an affinity about 0.7 of that of di(C18 : 1)PC. The structure of the peptide itself is important. The peptide Ac-KKGYL6WL8YKKA-amide (Y2L14) incorporated into bilayers of dinervonylphosphatidylcholine [di(C24 : 1)PC] whereas L16 did not incorporate into this lipid. It is suggested that thinning of a lipid bilayer around a peptide to give optimal hydrophobic matching is less energetically unfavourable when a Tyr residue is located in the lipid/water interfacial region.
authors.affiliation: Division of Biochemistry and Molecular Biology, School of Biological Sciences, University of Southampton, UK.
authors.forename: S
authors.initials: S
authors.lastname: Mall
authors.forename: R P
authors.initials: RP
authors.lastname: Sharma
authors.forename: J M
authors.initials: JM
authors.lastname: East
authors.forename: A G
authors.initials: AG
authors.lastname: Lee
mesh_terms: D002462:Cell Membrane / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D008567:Membranes, Artificial; D008954:Models, Biological; D008962:Models, Theoretical; D010455:Peptides
chemical_list: D008055:Lipids; D008565:Membrane Proteins; D008567:Membranes, Artificial; D010455:Peptides