E4 proteins

Of the several genotypes for apo E, the acquisition of two apo E s4 alleles may increase the risk for Alzheimer s disease up to eightfold. Each copy of the apo E gene increases the risk and shifts the onset to lower ages. The biochemical mechanism by which apo E e4 protein participates in formation of tangles and plaques is unclear. Several mechanisms have been suggested, namely, interaction with tau protein and generation, and clearance of A/3 peptides. 

A relationship with transmission of the Apo 4 allele has also been established. The ApoES binding to tau may regulate the function of tau. Apo 3 may act as a beneficial cofactor or a sequestration agent to prevent phosphorylation for a portion of the tau pool. This regulation would not be present in individuals who express only E4 protein [91],... 

AFP-EIA AFP-controlled E4 and E3 Artificial a-Fetoprotein promoter with enhancer and silencer elements to negate expression in86 deleted normal hepatocytes E4 proteins enhance cell lyses... 

Increased cholesterol concentrations have been associated with AD. The cholesterol increases P-amyloid protein synthesis which can lead to plaque formation.16 Also, the apo E4 allele is thought to be involved in cholesterol metabolism and is associated with higher cholesterol levels.16... 

Boc-E4 Boc-EAR lR-MCA BJP-B6 + MCA Autoantibodies Bence Jones proteins (BJPs) (monoclonal antibody light chains) isolated from the urine of multiple myeloma patients, were found to hydrolyse peptide methylcoumarin amide peptide-MCA substrates 1.5 x 101 3.3 X 1()-2 nr 5.8... 

Mann, D.M., Iwatsubo, T., Pickering-Brown, S.M., Owen, F., Saido, T.C., Perry, R.H. (1997) Preferential deposition of amyloid beta protein (Abeta) in the form of Abeta40 in Alzheimer s disease associated with a gene dosage effect of the apolipoprotein E E4 aUele. Neurosci. Lett., 221, 81-84. 

A number of useful reviews of small molecule-protein interaction have appeared (D2, E4, S26, W7), and these contain detailed treatments of the mathematical analysis of binding data as well as information on experimental methods. 

Although it has been shown that at least some of these polypeptides derive from exchange with the VLDL protein (E4, S22), a stringent chemical corroboration of these findings has not been published. Studies from these laboratories have now provided such a docmuentation at least in terms of polypeptides D, Dj, Dg, and D4 in apo VLDL (for properties, see below). Other minor polypeptides are also members of V, but their properties are still in the process of being defined (L2a). 

E4. Eisenberg, S., Bilheimer, D. W., and Levy, R. I., The metabolism of very low density lipoproteins proteins. II. Studies on the transfer of apoproteins between plasma lipoproteins. Biochim. Biophys. Acta 280, 94-104 (1972). 

The best purification procedure is one that yields a maximum amount ol the purified protein in a minimum amount of time. The following discussion outlines the basic steps that must be considered in order to develop a protein purification scheme (Table E4.1). 

The specific amino acid side chains on a-lactalbumin responsible for binding to the metal support are not known however, a-lactalbumin is a metalloprotein. Under physiological conditions, it carries one Ca(II) per molecule hence, there are metal binding sites on the protein. Column-bound a-lactalbumin is eluted by a solution of the free ligand imidazole. A flowchart outlining these procedures is shown in Figure E4.3. 

Study the destained gel or diagram and estimate the number of protein components in each sample. Calculate the relative mobility of each protein band using Equation E4.1. 

Prepare a standard calibration curve using the data obtained for standard gamma globulin (Table E4.2, tubes 2 to 6). Plot the absorbance on the j axis and mg of standard protein per assay on the x axis. Use the standard curve to calculate the protein concentration in the isolated a-lactalbumin fractions (in units of mg/mL.) Compare your graph with Figure 2.6. 

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