Apolipoprotein D in Lipid Metabolism and Its Functional Implication in Atherosclerosis and Aging

Perdomo, German; Dong, H. Henry

Second, apoD contributes to HDL remodeling via its covalent cross-link with apolipoprotein A-II (apoA-II), a structural component of HDL. Blanco-Vaca et al. [65] detect the presence of disulfide-linked heterodimers of apoD and apoA-II in human plasma. Non-reducing polyacrylamide gel electrophoresis demonstrates that the apoD-apoA-II heterodimer has an apparent molecular mass of 38 kDa, which is significantly larger than monomeric apoD (MW, 29 kDa). Sequence analysis reveals the presence of five cysteine residues in the human apoD protein. Mass Spectrometric analysis in combination with crystallographic studies of human apoD protein illustrates that four cysteines (Cys16-Cys41 and Cys8-Cys114) are primed for forming two intra-molecular disulfide bonds and the remaining unpaired cysteine (Cys-116) is responsible for intermolecular covalent cross-link with Cys-6 of apoA-II within HDL [31, 41] . Interestingly, the rodent apoD lacks the unpaired Cys-116, as it is replaced by threonine at the corresponding amino acid residue. Thus, the physiological significance of this covalent cross-link between apoD and apoA-II in HDL remodeling and cholesterol metabolism remains elusive [41] .