title: Protein-lipid interactions in reconstituted high density lipoproteins: apolipoprotein and cholesterol influence.
abstract: Two fluorescent probes-cis- and trans-parinaric acids were used to study the dimensions, lipid dynamics and apolipoprotein location in the reconstituted discoidal high density lipoproteins (rHDL). The rHDL particles made from apolipoprotein A-I (apoA-I), dipalmitoylphosphatidylcholine (DPPC), with or without cholesterol (Chol) were compared with the analogous particles with two other apolipoproteins-apoE and apoA-II. The data obtained for apoA-I-containing rHDL were as follows: (1) the inclusion of 8 mol.% of cholesterol did not significantly change the particle dimensions (13+/-1 nm) or the mean distance between apoA-I and the disc axis; (2) the phospholipid domains-boundary lipid region in the close vicinity to apoA-I molecule and the remaining part of the bilayer-existed at temperatures both lower and above DPPC transition temperature T(t); (3) at T<T(t) Chol molecules preferentially accumulated in the central area with a radius of 2.8 nm that conserved partially after DPPC phase transition; (4) inhomogeneous cholesterol distribution was assumed to exist within these domains. A hydrophobic matching concept was used to compare protein-lipid interactions in rHDL particles. For complexes with all three apolipoproteins studied, at T<T(t) the probe mobility in the lipid phase of rHDL was significantly higher compared to pure DPPC bilayer. After temperature-induced transition, mobility increased significantly still being lower in rHDL. The comparative study of lipid dynamics in apoA-I-, apoE- and apoA-II-containing complexes revealed the presence of boundary lipid in all three complexes without cholesterol. The degree of cholesterol exclusion from the boundary lipid region seems to increase in the order A-I<E<A-II for Chol-containing complexes, the exclusion being an inherent property of the particular apolipoprotein molecule.
authors.affiliation: National Research Centre for Preventive Medicine, 10, Petroverigsky Street, 101953 Moscow, Russia. dergunov@img.ras.ru
authors.forename: A D
authors.initials: AD
authors.lastname: Dergunov
authors.forename: G E
authors.initials: GE
authors.lastname: Dobretsov
authors.forename: S
authors.initials: S
authors.lastname: Visvikis
authors.forename: G
authors.initials: G
authors.lastname: Siest
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry* / Q000378:metabolism; D001053:Apolipoproteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002784:Cholesterol / Q000378:metabolism / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000493:pharmacokinetics; D005454:Fluorescence Polarization; D005456:Fluorescent Dyes / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry*; D008567:Membranes, Artificial; D008968:Molecular Conformation; D013696:Temperature
chemical_list: D001053:Apolipoproteins; D005231:Fatty Acids, Unsaturated; D005456:Fluorescent Dyes; D008075:Lipoproteins, HDL; D008567:Membranes, Artificial; D015060:1,2-Dipalmitoylphosphatidylcholine; D002784:Cholesterol; C013641:parinaric acid