COMPARISON OF THE STRUCTURAL AND FUNCTIONAL-EFFECTS OF MONOMERIC AND DIMERIC HUMAN APOLIPOPROTEIN A-II IN HIGH-DENSITY-LIPOPROTEIN PARTICLES

Citation
S. Lundkatz et al., COMPARISON OF THE STRUCTURAL AND FUNCTIONAL-EFFECTS OF MONOMERIC AND DIMERIC HUMAN APOLIPOPROTEIN A-II IN HIGH-DENSITY-LIPOPROTEIN PARTICLES, Lipids, 31(11), 1996, pp. 1107-1113
Citations number
42
Categorie Soggetti
Biology
Journal title
LipidsACNP
ISSN journal
00244201
Volume
31
Issue
11
Year of publication
1996
Pages
1107 - 1113
Database
ISI
SICI code
0024-4201(1996)31:11<1107:COTSAF>2.0.ZU;2-Z
Abstract
High density lipoprotein (HDL) is thought to play a significant role i n the process of reverse cholesterol transport. It has become clear th at the apolipoprotein (ape) composition of HDL is important in determi ning the metabolic fate of this particle. The major proteins of human HDL are apoAI and APOAII; the latter protein is a disulfide-linked dim er in humans and higher primates but monomeric in the other species. T he consequences of the apo Cys6-Cys6 disulfide bridge in apoAII for hu man HDL structure and function are not known. To address this issue, t he influence of the Cys6-Cys6 disulfide bridge on the interaction of h uman apoAII with palmitoyl-oleoyl phosphatidylcholine has been studied . The size and valence of a series of homogeneous discoidal complexes containing either monomeric (reduced and carboxymethylated) or dimeric apoAII have been determined, and their ability to remove cholesterol from rat Fu5AH hepatoma cells grown in culture has been compared. The apoAII dimer and monomer form discoidal complexes of similar size, wit h twice as many of the latter molecule required per disc. Removal of t he disulfide bond influences the stability of the helical segments aro und the edge of the disc as seen by a decrease in alpha-helix content of the monomeric protein. The discoidal particles containing the monom eric form of apoAII are somewhat more effective than particles contain ing either dimeric apoAII or apoAI in removing cellular cholesterol. O verall, reduction of the disulfide bridge of apoAII probably does not have a major effect in the determination of HDL particle size in vivo. It follows that the evolution of the Cys6-Cys6 disulfide bond in high er primates probably has not had a major effect on the function of the apoAII molecule.