title: Activation of lecithin cholesterol acyltransferase by a disulfide-linked apolipoprotein A-I dimer.
abstract: Apolipoprotein A-IMilano is a molecular variant of apoA-I, containing the Arg173-->Cys substitution that forms a disulfide linked homodimer (A-IM/A-IM). To assess the effect of this structural modification on a major function of the apolipoprotein, its activation of lecithin cholesterol acyltransferase (LCAT), we prepared well-defined complexes of A-IM/A-IM and apoA-I with phospholipids and cholesterol and compared their reactivities with LCAT. Particles with A-IM/A-IM had very similar diameters to apoA-I particles (7.8 and 12.5 nm) but had distinct apolipoprotein and phospholipid contents and protein secondary structures; they bound LCAT with comparable affinities, but were less efficient substrates for the enzyme (40 to 70% less reactive). We conclude that the local structural constraints in A-IM/A-IM do not prevent the formation of well-defined complexes with phospholipids and do not influence the binding of the enzyme to the particles, but have an inhibitory effect on LCAT activation.
authors.affiliation: Center E. Grossi Paoletti, University of Milano, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Calabresi
authors.forename: G
authors.initials: G
authors.lastname: Franceschini
authors.forename: A
authors.initials: A
authors.lastname: Burkybile
authors.forename: A
authors.initials: A
authors.lastname: Jonas
mesh_terms: D016632:Apolipoprotein A-I / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry*; D004789:Enzyme Activation / Q000187:drug effects; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000138:chemical synthesis / Q000737:chemistry; D010316:Particle Size; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016632:Apolipoprotein A-I; D004220:Disulfides; D008075:Lipoproteins, HDL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase