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

Perdomo, German; Dong, H. Henry

ApoD is an atypical apolipoprotein of 169 amino acids. Unlike canonical apolipoproteins that are produced mainly in liver and intestine, apoD is expressed widely in mammalian tissues including brain, liver, intestine, cardiac and skeletal muscle, adipose tissue, and pancreas [34] [35] [36] (Fig. 2) . ApoD does not share significant degrees of homology in the amino acid sequence with other apolipoproteins. Instead, apoD is structurally similar to the lipocalin family of proteins. This superfamily comprises a diverse class of lipidbinding proteins including fatty acid binding proteins (FABPs), plasma retinol-binding proteins (RBP) and apolipoprotein M (apoM) [34, [37] [38] [39] . Despite their dissimilarities in amino acid sequences, the lipocalin superfamily of proteins share a highly conserved βbarrel structure that is comprised of an eight-stranded anti-parallel β-sheet [40] . Such a tertiary architecture is predicted to form a ligand-binding pocket that is thought for binding and transporting lipids and other small hydrophobic molecules [34, 37] . This characteristic lipocalin fold is validated for apoD by Eichinger et al. [41] , who recently crystalized the human apoD protein in its free form and in complex with progesterone. Cystallographic studies reveal that the eight-stranded anti-parallel β-sheets of apoD are connected by four loops in a pair-wise manner, forming a conically shaped cavity that is capable of binding hydrophobic ligands [40, 41] . Consistent with its structural organization, apoD is shown to associate with a number of ligands including cholesterol, progesterone, pregnenolone, bilirubin and arachidonic acid [13, 34] .