Recombinant Human Apolipoprotein E3 Protein, CF

ApoE is a major protein component of serum LDL, VLDL, HDL, and chylomicrons. It is produced predominantly by hepatocytes, macrophages, and non-neuronal cells in the CNS. ApoE-containing particles transport triglycerides and cholesterol to peripheral tissues for cellular uptake and catabolism (1 - 4). Mature human ApoE is a 34 kDa glycoprotein that consists of an N-terminal domain composed of four bundled alpha -helices, plus a hinge region and an extended alpha -helical C-terminal domain (2, 5). Its amphipathic nature and flexible structure enables it to adopt dramatically different conformations upon lipid association (2). ApoE is monomeric in lipid particles, although it forms oligomers when lipid-free (6). ApoE3 is the most abundant of the three common alleles in human; ApoE2 and ApoE4 differ by single aa substitutions (1). Mature human ApoE shares 71% aa sequence identity with mouse and rat ApoE. LDL receptor family proteins preferentially bind and internalize the lipid-bound form of ApoE with the exception of VLDLR which also efficiently internalizes lipid-free ApoE (7, 8). Lipoprotein uptake is facilitated by the initial binding of ApoE to cell surface heparan sulfate proteoglycans (HSPG) (9). Receptor/HSPG binding and lipid interactions primarily involve the N- and C-terminal regions of ApoE, respectively (2). Recycled lipid-free ApoE is formed into HDL particles through interactions with the lipid transporter ABCA1 (10). High cellular sterol content activates the nuclear hormone receptor LXR which promotes increased ApoE synthesis and increased sterol efflux, while low sterol content induces LDL R expression with increased sterol uptake and decreased ApoE production (11). ApoE3 dampens the TNF-alpha induced inflammatory response in vascular endothelial cells (12). In the CNS, ApoE blocks production of the amyloid A beta peptide by inhibiting the gamma -secretase cleavage of APP (13). It also complexes with A beta and promotes A beta internalization via LRP2 (14, 15).

• Apolipoprotein E3/ApoE3 Proteins and Enzyme