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
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.