Apolipoproteins, functions structural

FIGURE 9-1. Lipoprotein structure. Lipoproteins are a diverse group of particles with varying size and density. They contain variable amounts of core cholesterol esters and triglycerides, and have varying numbers and types of surface apolipoproteins. The apolipoproteins function to direct the processing and removal of individual lipoprotein particles. (Reprinted from LipoScience, Inc. with permission.)... 

Interactions of apolipoproteins with PL are essential for the assembly of lipoproteins, stabilization of lipoprotein structures, and expression and modulation of apolipoprotein functions. The main experimental approaches for the study of apolipoprotein interactions with PL have used isolated, exchangeable apolipoproteins in conjunction with aggregated lipids dispersed in water or spread at the air-water interface. The aggregated lipid states include lipid monolayers, various types of liposomes (small unilamellar vesicles, large unilamellar vesicles, multilamellar vesicles), and emulsions. All these lipid systems consist of or include PL, especially PC. 

Hatters, D.M., Peters-Libeu, C.A., Weisgraber, K.H. 2006. Apolipoprotein E structure insights into function. Trends Biochem. Sci. 31 445-454. 

Jonas, A. 1992. Lipid-binding properties of apolipoproteins. In Structure and Function of Apolipoproteins. M. Rosseneu, editor. Boca Raton, FL CRC Press, pp. 217-250. 

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). 

R15. Rosseneu, M., and Labeur, C., Apolipoprotein structure, function and measurement. Curr. Opin. Lipidol. 1, 508-513 (1990). 

In the review dealing with the proteins of plasma lipoproteins, Scanu and Ritter have produced a most lucid and detailed discussion of recent advances in this difficult field. An exciting account is given of the isolation of apolipoproteins, their chemical structure, and what is known of their biological functions lipoproteins relevant to patients with dyslipo-proteinemia are also described. 

The molecular basis for the association between apoE4 and Alzheimer s disease is not yet known. Speculation has focused on a possible role for apoE in stabilizing the cytoslceletal structure of neurons. The apoE2 and apoE3 proteins bind to a number of proteins associated with neuronal microtubules, whereas apoE4 does not. This may accelerate the death of neurons. Whatever the mechanism proves to be, these observations promise to expand our understanding of the biological functions of apolipoproteins. 

Apolipoproteins The apolipoproteins associated with lipoprotein particles have a number of diverse functions, such as providing recognition sites for cell-surface receptors, and serving as activators or coenzymes for enzymes involved in lipoprotein metabolism. Some of the apolipoproteins are required as essential structural components of the particles and cannot be removed (in fact, the particles cannot be produced without them), whereas others are transfered freely between lipoproteins. Apolipoproteins are divided by structure and function into five major classes, A through E, with most classes having subclasses, for example, apo A-l and apo C-ll. [Note Functions of all of the apolipoproteins are not yet known.]... 

Weinberg RB, Jordan MK, Steinmetz A. Distinctive structure and function of human apolipoprotein variant ApoA-IV-2. J Biol Chem. 1990, 265 18372-18378. 

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.

Apolipoprotein C-II can also be isolated from VLDL or HDL (H20, L5, N3). It contains 78 residues (J3) and has been shown by Chou-Fasman analysis to bind phospholipids (M26, M40), with three predicted helical sequences (M26). ApoC-II has attracted a great deal of attention because it activates one of the most important enzymes in plasma lipid metabolism, lipoprotein lipase, responsible for the hydrolysis of triglyceride in chylomicrons and VLDL. Sparrow and Gotto have summarized a number of studies on structure-function relationships (S52). These, taken together, indicate that there are separate functional domains in apoC-II, in that lipoprotein lipase activation is mediated by residues 55-78 and phospholipid binding by... 

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