Lipoprotein subunits

B. The Benson Lipoprotein Subunit Model. Here, the proteins are globular and the membrane is a protein-lipid mixture. The hydrophobic tails of the lipids are embedded in the hydrophobic parts of the proteins. The lipid head groups are exposed to the solvent. There is no lipid bilayer. 

With this state of uncertainty, it is not possible to define the true structural and functional role of the chylomicron protein. Chylomicrons are generally considered as a large central sphere of glycerides with small amounts of cholesterol, phospholipid, and protein loosely adsorbed on the surface, forming, according to Lindgren and Nichols (1960), small lipoprotein subunits. Aside from physical stabilization, the adsorbed components at the surface appear to impart biochemical specificity to the chylomicron particles, as indicated by Korn s studies (1955) showing that chylomicrons, and not simple fat emulsions, form an optimal substrate for the enzyme lipoprotein lipase. 

Several studies have shown (cf. review by Bakerman and Wasem-iller, 1967 Engelman et al., 1967 Terry et al., 1967 Engelman and Morowitz, 1968a,b) that membrane dissociation could be limited to the separation of lipoprotein subunits by the use of appropriate agents and conditions. On the other hand, the use of selected solvents has permitted the isolation and study of structural protein. Data from such investigations made with erythrocyte membranes constitute the most complete set available (Bakerman and Wasem-iller, 1967 Zahler, 1968) and for this reason will be used in the following analysis of membrane dissociation mechanism. 

Fig. 12. Lipoprotein subunits in the classieal model. Superstruetural elements have not been represented in siuface protein units, U. L is lipid component. Model (a) is equivalent to (b) (see text) showing subunits LU. (e) Intiasubunit, and (d) intersubunit cohesional forces. Forces i, ii, iii, iv, and v described in text are localized as shown. D indicates position of divalent cation bridges.

Hence/ = 6.4, showing that total intmsubunitcohesion is appreciably higher than intersubunit bonding. A molecular weight of the monomeric protein unit as low as 6400 would correspond to / = 2 still justifying the existence of distinct lipoprotein subunits of diameter = 37 A. 

Since it is unlikely that the basic assumption in the above derivation could lead to much overestimation of ratio / it must be concluded that the lipoprotein subunit concept is inherent to the Danielli model. As shown below, this concept, which does not entail any structural change of the classical model, is fundamental in interpreting a large number of data through this model. 

Concentrated acetic acid (Table IV, 7) probably induced considerable dissociation of lipoprotein subunit components. This solvent falls in the group used by Zahler (1968) (Table IV, 6) for this very purpose. 

In the case of Kavanau s ingenious disc-and-pillar - variable pore hypothesis the fault appears to lie, not in mechanisms as described, but in the fact that the protein component in lipoprotein subunits would be responsible for a great number of complex functions required by the proposed mechanism. The sum of specific properties encoded in the amino acid sequence of this protein would be exceedingly large. 

In this demonstration, the lipoprotein subunit concept is inherent to the classical model and applies to a wide range of subunit dimensions and shapes (Section III, B, 1). 

MTP is responsible for the transfer of TGs and cholesteryl esters from the endoplasmic reticulum (ER) to lipoprotein particles (VLDL in hepatocytes in the liver and chylomicrons in endocytes in the intestine) for secretion [52]. It is a heterodimer consisting of a unique large subunit essential for lipid transfer encoded by the mttp gene and a smaller subunit, the ubiquitous ER enzyme protein disulfide isomerase [53]. 

El. Edelstein, C., Lim, C. T., and Scanu, A. M., On the subunit structure of the protein of human serum high density lipoprotein. I. A study of its major polypeptide component (Sephadex, fraction III). J. Biol. Chem. 247, 5842-5849 (1972). 

R7. Rudman, D., Garcia, L. A., and Howard, C. H., A new method for isolating the non-identical protein subunits of human plasma a-lipoprotein. J. Clin. Invest. 49, 365-372 (1970). 

Shore, B., and Shore, V., Heterogeneity in protein subunits of human serum high density lipoproteins. Biochemistry 7, 2773-2777 (1968). 

Kishimoto, A. Goldstein, J.L. Brown, M.S. Purification of catalytic subunit of low density lipoprotein receptor kinase and identification of heat-stable activator protein. J. Biol. Chem., 262, 9367-9373 (1987)... 

Another acute-phase protein, C-reactive protein, may interact with VLDL. Purified C-reactive protein is composed of five noncovalently-associ-ated subunits (Mr each about 21,000). The complex with VLDL appears to be destroyed by ultracentrifugal isolation of lipoproteins, or chelation with EDTA (Cl). 

Protein generally lipoprotein or glycoprotein in nature Typical molecular weight in the range of 45-200 kDa Can be composed of subunits Frequently glycosylated... 

In ABL, an early step in apoB lipoprotein assembly shared by intestinal and liver cells is defective. The net result is near absence of all plasma apoB lipoproteins. ApoB synthesis from a mRNA transcript occurs, but its successful assembly into the mature lipoprotein particle does not. The inability to assemble apoB into lipoproteins was shown to be due to a defect in the mttp gene in affected individuals (Wetterau et al., 1992). Its translational product is an 894-amino acid, 97-kd, polypeptide that exists in the ER complexed with a 55-kd protein disulfide isomerase which is believed to maintain solubility, physiologic activity, and ER retention of the 97-kd peptide. The heterodimeric complex of the 97-kd and 55-kd subunits is referred to as microsomal triglyceride transfer protein (MTP) (Wetterau et al., 1992). 

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