Apolipoprotein lipid binding

Bultel-Brienne, S, Lestavel, S, Pilon, A, Laffont, I, Tailleux, A, Fruchart, JC, Siest, G, and Clavey, V, 2002. Lipid free apolipoprotein E binds to the class B type I scavenger receptor I (SR-BI) and enhances cholesteryl ester uptake from hpoproteins. J Biol Chem 277, 36092-36099. 

Cl. Camejo, G., Suarez, Z. M., and Munoz, V., The apolipoproteins of human plasma high density lipoprotein a study of their lipid-binding capacity and interaction with lipid monolayers. Biochim. Biophys. Acta 218, 155-166 (1970). 

The major lipoproteins of insect hemolymph, the lipophorins, transport diacylglycerols. The apolipo-phorins have molecular masses of -250, 80, and sometimes 18 kDa.34-37a The three-dimensional structure of a small 166-residue lipophorin (apolipophorin-III) is that of a four-helix bundle. It has been suggested that it may partially unfold into an extended form, whose amphipathic helices may bind to a phospholipid surface of the lipid micelle of the lipophorin 35 A similar behavior may be involved in binding of mammalian apolipoproteins. Four-helix lipid-binding proteins have also been isolated from plants.38 See also Box 21-A. Specialized lipoproteins known as lipovitellins... 

MSP1 (200 residue lipid-binding domain of human apolipoprotein Al)90 PEG precipitate of nanodiscs 0.3-0.5 ppm 263 K gas 283 K sample Signals broaden at lower temperatures... 

Apolipoprotein C-I can be isolated from VLDL (B56, S52) or HDL (08) by repeated chromatography. It has been sequenced and found to contain 57 residues (J8, S33). It appears to be highly helical on lipid binding (J7), with three lipid-binding helical sequences predicted by Chou-Fasman analysis (S22). Both native and synthetic apoC-I bind lipid, and also activate LCAT (H7, S34, S46). This dual activity is probably due to the peptide which contains amino acids 17-57 this sequence appears to activate LCAT, and the sequence 32-57 appears to bind lipid (S49). ApoC-I readily selfassociates in aqueous solution (07). 

J6. Jackson, R. L., Morrisett, J. D., Pownall, H. J., and Gotto, A. M., Jr., Human high density lipoprotein, apoliprotein glutamine II. The immunochemical and lipid-binding properties of apolipoprotein glutamine II derivatives. J. Biol. Chem. 248, 5218-5224 (1973). 

Figure 1. Open conformation model of exchangeable apolipoproteins upon lipid-binding.

The amphipathic helix, in which residues are spaced so that the helical periodicity places hydrophobic side chains on one side of the helix and hydrophilic side chains on the other, is a common structural motif used by the peripheral apolipoproteins to bind lipid (Segrest et al., 1992) it is also a structural element present in globular proteins (Perutz et al., 1965). 

In addition to the well-known functions of apolipoproteins in lipid binding and solubilization, modulation of enzymatic activities, and receptor recognition, other functions have been described for apolipoproteins. For example, apo E has been implicated in nerve repair and regeneration as well as in plaque formation in Alzheimer s disease. Apo... 

The exchangeable apolipoproteins, devoid of lipids, have substantial amounts of a-helical structure in physiological aqueous solutions and their a-helix content increases markedly upon lipid binding. For example, apo A1 is about 50% helical in the lipid-free state, and becomes 60-85% helical when bound to lipids, as measured by circular dichroism... 

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. 

Fig. 4. Helical wheel presentation of the presumed structure of segment 167-184 of apolipoprotein A-I. In the Apo A-I-I ano mutant, Arg is substituted with cysteine. This substitution leads to the disappearance of an ion pair, Glu -Arg with a resulting loss in amphipathic structure and lipid binding capacity [11]...

Apolipoprotein A-I (apoA-I). A small lipid-binding peptide associated with almost all HDL. 

Apolipoprotein A lipid-binding protein that mediates the transport of lipid molecules through aqueous media. The association of apolipoproteins with lipids form a lipoprotein particle. 

Figure 26-5. Factors affecting cholesterol balance at the cellular level. Reverse cholesterol transport may be initiated by pre 3 HDL binding to the ABC-1 transporter protein via apo A-l. Cholesterol is then moved out of the cell via the transporter, lipidating the HDL, and the larger particles then dissociate from the ABC-1 molecule. (C, cholesterol CE, cholesteryl ester PL, phospholipid ACAT, acyl-CoA cholesterol acyltransferase LCAT, lecithinicholesterol acyltransferase A-l, apolipoprotein A-l LDL, low-density lipoprotein VLDL, very low density lipoprotein.) LDL and HDL are not shown to scale.

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). 

The method utilizing ID NMR is simple and eonvenient. Henee the NMR method diseussed here ean be applied to the systematie investigation of the membrane irug inter-aetions, elosely related to the vital function in biomembranes. It is expected that the application can be extended to the lipid-peptide interaction and protein uptake. We are now applying the method to apolipoprotein binding with lipid bilayers and emulsions. Preferential protein binding sites in membranes can be specified by NMR on the molecular level. 

Mann, W.A., Meyer, N., Weber, W., Meyer, S., Greten, H., and Beisiegel, U. (1995) Apolipoprotein E isoforms and rare mutations parallel reduction in binding to cells and to heparin reflects severity of associated type III hyperlipoproteinemia./. Lipid Res. 36, 517. 

---