Exchangeable apolipoproteins (apoA, apoC and apoE) have the same genomic structure and are members of a multi-gene family that probably evolved from a common ancestral gene. This entry includes the ApoA1, ApoA4, Apo5 and ApoE proteins. ApoA1, ApoA4 and Apo5 are part of the APOA1/C3/A4/A5 gene cluster on chromosome 11 []. Apolipoproteins function in lipid transport as structural components of lipoprotein particles, cofactors for enzymes and ligands for cell-surface receptors. In particular, apoA1 is the major protein component of high-density lipoproteins; apoA4 is thought to act primarily in intestinal lipid absorption; and apoE is a blood plasma protein that mediates the transport and uptake of cholesterol and lipid by way of its high affinity interaction with different cellular receptors, including the low-density lipoprotein (LDL) receptor. Recent findings with apoA1 and apoE suggest that the tertiary structures of these two members of the human exchangeable apolipoprotein gene family are related []. The three-dimensional structure of the LDL receptor-binding domain of apoE indicates that the protein forms an unusually elongated four-helix bundle that may be stabilised by a tightly packed hydrophobic core that includes leucine zipper-type interactions and by numerous salt bridges on the mostly charged surface. Basic amino acids important for LDL receptor binding are clustered into a surface patch on one long helix [].
