Apolipoprotein B Structure

The length of the chromatin loop containing the human apoB gene was determined by locating three nuclear matrix attachment sites, two at the 5 end and one at the 3 end. At the 5 end, the distal site was located between nucleotides -5262 and -4048, and the proximal site, between -2765 and -1801. At the 3 end, a single site was found between +43,186 and +43,850. HepG2 cells, which express the apoB gene, contained all three sites whereas HeLa cells, which do not express apoB, lacked the 5 distal site (Levy-Wilson and Fortier, 1989). 

A substantial number of common polymorphisms are associated with the human apoB gene, and Table I lists those which have been reported more than once. These have proved valuable in genetic (Young et ai, 1986), anthropological (Rapacz etai, 1991), forensic (Butler, 1990), and medical studies (Soria et ai, 1989). 

Common coding sequence polymorphisms (observed more than once) Restriction Exon Common name Amino acids Residue no. endonuclease Ref.  

Common polymorphisms located outside the coding sequence  

The processed mRNA transcribed from the human apoB gene contains 14,121 and 14,112 nucleotides (Cladaras /a/., 1986), depending on the presence or absence of a 9-nucleotide insertion/deletion polymorphism in the signal sequence (Boerwinkle and Chan, 1989). Messenger 

---

S.O. Olofsson, G. Bjursell, K. Bostrom, P. Carlsson, J. Elovson, A.A. Protter, M.A. Reuben and G. Bondjers, Apolipoprotein B structure, biosynthesis and role in the lipoprotein assembly process, Atherosclerosis 68 (1987) 1-17. 

Richardson, P.E., Manchekar, M., Dashti, N., Jones, M.K., Beigneux, A., Young, S.G., Harvey, S.C., Segrest, J.P. 2005. Assembly of lipoprotein particles containing apolipoprotein-B structural model for the nascent lipoprotein particle. Biophys. J. 88 2789-2800. 

Lipoprotein fraction containing triglycerides and to a lesser degree cholesterol. VLDL is produced by the liver. The main structural protein connected to this lipoprotein class is apolipoprotein B. 

In contrast to MDA and hydroxynonenai, other aldehyde products of lipid peroxidation are hydrophobic and remain closely associated with LDL to accumulate to mil-limolar concentrations. Aldehydes at these elevated levels react with the protein portion of the LDL molecule, apolipoprotein B (apoB). Accumulated aldehydes bind the free amino groups from lysine residues in addition to other functional groups (-OH, -SH) on the apoB polypeptide. Consequently, the protein takes on a net negative charge and complete structural rearrangement results in the formation of ox-LDL. ox-LDL is no longer recognized by the LDL receptor, and has several pro-inflammatory properties (discussed below). 

Each lipoprotein has various proteins called apolipoproteins embedded on the surface (Fig. 9-1). These apolipoproteins serve four main purposes, they (1) are required for assembly and secretion of lipoproteins (such as apolipoproteins B-48 and B-100) (2) serve as major structural components of lipoproteins ... 

Fatty liver occurs in kwashiorkor, probably due to lack of protein in the diet, which reduces the synthesis of the structural protein for VLDL (apolipoprotein B). The increased triacylglycerol produced in the liver from fatty acids removed from the blood (i.e. the inter-tissue triac-... 

Apolipoprotein B. Apo B is a structural apolipoprotein for chylomicrons, VLDL, and LDL particles. It is synthesized in enteric and hepatic cells. It is important for cholesterol transport to cells via interaction with LDL receptors. Nowadays, it seems its clinical relevance in CSF investigation is near Apo A-I and Apo A-II, but in current studies some varieties can be found (A23, T3). 

FIGURE 21-39 Lipoproteins. (a) Structure of a low-density lipoprotein (LDL). Apolipoprotein B-100 (apoB-100) is one of the largest single polypeptide chains known, with 4,636 amino acid residues (M, 513,000). (b) Four classes of lipoproteins, visualized in the electron... 

Fig. 9. RNA editing, (a) Unedited apolipoprotein B mRNA is translated to yield ApoB-100, a 4536-amino acid long polypeptide with structural domains for lipoprotein assembly and receptor binding functions (b) translation of the edited mRNA yields the shorter ApoB-48 which lacks the receptor binding domain.

Special proteins, called apolipoproteins, are required for handling and transport of lipid droplets. These proteins are synthesized on the ER and enter the lumen of the ER, where they are assembled into large macromolecular structures. The relevant proteins include apolipoprotein A (apo A) and apolipoprotein B (apo B). Apo A and apo B combine with lipid droplets to form structures called chylomicrons, microscopic particles with large cores of lipid coated with a thin shell of protein. The chylomicrons are transferred to secretory vesicles, which migrate through the cytoplasm to the basal membrane of the cell. Here the vesicles fuse with the membrane, resulting in the expulsion of chylomicrons from the cell. (If the vesicles fused with the apical membrane of the enterocyte, the effect would be a futile transfer of the dietary lipids back to the lumen of the small intestine.)... 

APOLiPOPROTEIN B AND LOW-DENSITY LIPOPROTEIN STRUCTURE IMPLICATIONS FOR BIOSYNTHESIS OF TRIGLYCERIDE-RICH LIPOPROTEINS... 

IV. Structural Studies of Apolipoprotein B on Low-Density Lipoprotein Surfaces... 

Nielsen, L. B., Kahn, D., Duell, T., Weier, H. U., Taylor, S., and Young, S. G. 1998. Apolipoprotein B gene expression in a series of human apolipoprotein B transgenic mice generated with recA-assisted restriction endonuclease cleavage-modified bacterial artificial chromosomes. An intestine-specific enhancer element is located between 54 and 62 kilobases 5 to the structural gene, J. Biol. Chem., 273, 21800-21807. 

Apolipoproteins are structural components of plasma lipoproteins, and they maintain the integrity of the lipoproteins through the interactions with the hydrophilic core and the surrounding aqueous environments. These apolipoproteins act as ligands for specific cell receptors and activators or inhibitors for enzymes involved in lipoprotein metabolism. There are at least 11 apolipoproteins, which differ in molecular mass (from 6.5 to 600 kDa) and amino-acid composition, and they form less than 2 g/L of normal plasma protein. The apolipoprotein classes are designated by letters of the alphabet—A, B, C, D, and E—and numerals for subclasses (e.g., apo C-II). 

---