Lipoprotein, structure model

Fig. 2. A model for lipoprotein structure based on the interactions between apolipopro-teins and lipid constituents. The surface monolayer is composed of phospholipids and apolipoproteins. The apoproteins contain helical regions which are amphipathic. The hydrophobic surface of the amphipathic helix interacts with the fatty acyl chains of phospholipids, and the hydrophilic surface is exposed to the aqueous environment of the polar head groups and the plasma. Adapted from Pownall et al.. (1981).

The elucidation of the structure of any lipoprotein, i.e., the organization of the protein and lipid components, is a challenging problem, because it relies on several techniques that give only partial and approximate information. Structural models should be consistent with experimental data that characterize the physiological role and the physicochemical properties of the lipoprotein and its components. Considerable effort has been expended to fit experimental data to structural models of mammalian lipoproteins (Zilversmit, 1965 Sata et al., 1972 Schneider et al., 1973 Havel, 1975 Verdery and Nichols, 1975 Shen et al., 1977 ... 

Among the problems involved in constructing a general model for vertebrate lipoprotein structure, some of the more important are the heterogeneity in size and apolipoprotein composition and the small number of examples of lipoproteins containing similar apolipoprotein composition, which can be used to validate the model. Thus, in most cases, data as elementary as the stoichiometry of the apolipoproteins cannot be included in the models (Shen et ai, 1977) or, if stoichiometry data are included, only a partial fit of the data to the model is observed (Edelstein etal., 1979). 

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. 

No unique structural model for the plasma membrane can yet be deduced from these data (Korn, 1967) but it is now possible to consider that lipoprotein molecules may be the fundamental structural, as well as functional, components of membranes. Individual protein molecules could easily extend through the 75-100 A width of the plasma membrane. This implies that the carrier molecule and the structural molecule may be identical and that transport across the plasma membrane might be conceived as a conformational change of the membrane substructure. The membrane need no longer be viewed primarily as an inert barrier but rather as a dynamic aggregate of functional polymers (Korn, 1967). 

The cammon features of plasma lipoprotein structure are shown in Fig. 2. The interior of the lipoproteins contains the neutral lipids, cholesteryl ester and triglyceride. The exterior surface is a monomolecular film of specific proteins, termed apolipopro-teins, and the polar lipids, phosphatidylcholine and cholesterol. One possible arrangement (Edelstein et al., 1979) of the phosphatidylcholine, cholesterol and apolipoprotein A-1 (apoA-1) in HDL the most abundant of the plasma lipoproteins, is illustrated schematically in Fig. 3. In this model, there are no lipid domains in the surface of HDL. The phospholipid molecules are widely dispersed so that intermolecular associations can involve only apoprotein lipid and apoprotein apoprotein interactions. By contrast, with increasing size and a greater proportion of hydrophobic core volume, the structure of the larger lipoproteins more closely re-... 

The structure activity relationship (SAR) and animal model studies of biaryl benzamide MTP inhibitors 3 and 4 have also been reported. Compound 3 has an IC50 of 0.5 nM against human MTP in an in vitro assay and showed normalization of plasma lipoprotein levels in Watanabe-heritable hyperlipidemic rabbits,... 

ApoA-1 is the major structural lipoprotein component of HDL particles. Transgenic over-expression of apoA-1 has been well documented to correlate very strongly with antiatherogenic effects seen in a number of animal models [89-91]. The genetic deficiency of apoA-1 in humans has also been linked to low levels of HDL and premature atherosclerosis [90-92]. It is believed that infusion of apoA-1 enhances the ABCAl-mediated cholesterol efflux from macrophages [93]. During the last decade, significant efforts have been spent to find small... 

Loading of guests within the SCKs (for potential delivery) is modeled after lipoproteins, which are composites of cholesterol, cholesteryl ester, phospholipids, and protein forming biological structures of core-shell morphology... 

To better understand the structural properties of the lipoproteins involved in intracellular signaling pathways, synthetic lipopeptides are required as model compounds. In this context, to bypass the enzyme-catalyzed lipidation occurring in nature, optimized synthetic procedures have been elaborated for the more simple lipo-derivatives (for comprehensive reviews see ref[1]). However, similar efficient synthetic procedures for the glycosylphosphatidylinositol anchor are still lacked. 

Part of a lipoprotein particle. A model of the structure of apolipoprotein A-I (yellow), shown surrounding sheets of lipids. The apolipoprotein is the major protein component of high-density lipoprotein particles in the blood. These particles are effective lipid transporters because the protein component provides an interface between the hydrophobic lipid chains and the aqueous environment of the bloodstream. [Based on coordinates provided by Stephen Harvey.]... 

These data demonstrate that lipoprotein core circumference is directly proportional to apoB molecular weight (Fig. 13B). What is the interpretation of this relationship in terms of molecular structure Spring et al. (1992a,b) suggested that it is best explained by a beltlike model for apoB, because the circumference of any object is directly proportional to the mass of the belt that surrounds it. Thus, a third, independent approach has yielded a beltlike model for apoB on the surface of small emulsion particles. 

Fig. 1. General oil-droplet model of lipoproteins is presented for chylomicron, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) structures. Apolipoproteins in the outer phospholipid membrane, designated by letters, are defined in Table II. The major differences between the lipoproteins are the size of the neutral lipid (triglyceride and esterified cholesterol) core, liquid composition in the core, and apolipoprotein composition. (E) Triglycerides, ( Q ) phospholipids, and ( -) esterified cholesterol are shown. Although not shown, unesterified cholesterol is found predominantly in the phospholipid monolayer.

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