Apolipoproteins amphipathic

Dimyristoyl-PC liposomes can bind apolipoproteins reversibly, as described in the preceding section however, at the transition temperature of the lipid (24°C) and at sufficiently high proportions of apolipoprotein to dimyristoyl-PC (1/3 or greater, wt/wt), the apolipoproteins can solubilize the liposomes to give rise to small discs analogous to nascent HDL. The rate of the liposome disruption and solubilization depends on the temperature of the reaction. It is highest at the onset of the main phase transition of dimyristoyl-PC (when lattice defects in the PC bilayer, into which apolipoprotein amphipathic helices can penetrate, are maximal) and decreases a thousand-fold on either... 

The main transport form of lipids in the cir culation. They are spherical macromolecules of 10-1200 nm diameter-composed of a core of neutral lipids (mostly cholesterol ester and triglycerides) surrounded by an amphipathic shell of polar phospholipids and cholesterol. Embedded in the shell of lipoproteins are apolipoproteins that are essential for assembly of theparticles in tissues that secrete lipoproteins, and for their recognition by target cells. 

The nonpolar lipid core consists of mainly triacylglycerol and cholesteryl ester and is surrounded by a single surface layer of amphipathic phospholipid and cholesterol molecules (Figure 25-1). These are oriented so that their polar groups face outward to the aqueous medium, as in the cell membrane (Chapter 14). The protein moiety of a lipoprotein is known as an apo-lipoprotein or apoprotein, constituting nearly 70% of some HDL and as litde as 1% of chylomicrons. Some apolipoproteins are integral and cannot be removed, whereas others are free to transfer to other hpoproteins. 

Lipoproteins are an important class of serum proteins in which a spherical hydrophobic core of triglycerides or cholesterol esters is surrounded by an amphipathic monolayer of phospholipids, cholesterol and apolipoproteins (fatbinding proteins). Lipoproteins transport lipid in the circulation and vary in size and density, depending on their proteindipid ratio (Figure 7.3). Lipoprotein metabolism is adversely affected by obesity low-density lipoprotein (LDL)-cholesterol and plasma triglyceride are increased, together with decreased high-density lipoprotein (HDL)-cholesterol concentrations. 

Lam CW, Yuen YP, Cheng WF, Chan YW, Tong SF (2006) Missense mutation Leu72Pro located on the carboxyl terminal amphipathic helix of apolipoprotein C-II causes familial chy-lomicronemia syndrome. Clin Chim Acta 364 256-259... 

The plasma lipoproteins include chylomicrons, very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). They function to keep lipids (primarily triacylglyc-erol and cholesteryl esters) soluble as they transport them between tissues. Lipoproteins are composed of a neutral lipid core (containing triacylglycerol, cholesteryl esters, or both) surrounded by a shell of amphipathic apolipoproteins, phospholipid, and nonesterified cholesterol. Chylomicrons are assembled in intestinal mucosal cells from dietary lipids (primarily, triacylglycerol) plus additional lipids synthesized in these cells. Each nascent chylomicron particle has one molecule of apolipoprotein B-48 (apo B-48). They are released from the cells into the lymphatic system and travel to the blood, where they receive apo C-ll and apo E from HDLs, thus making the chylomicrons functional. Apo C-ll activates lipoprotein lipase, which degrades the... 

Lipoproteins are composed of a neutral lipid core (containing triacylglycerol, cholesteryl esters, or both) surrounded by a shell of amphipathic apolipoproteins, phospholipid, and nonesterified cholesterol. 

Apolipoprotein A-I is the primary protein component of HDL.23 2513 Most of the 243 residues consist of a nearly continuous amphipathic a helix with kinks at regularly spaced proline residues.26 28 Two disulfide-linked ApoA-I molecules may form a belt that encircles the discoid lipoprotein.2513 ApoA-II is the second major HDL protein, but no dearly specialized function has been identified.29 30 ApoA-I, II, and IV, apoC-I, II, and III, and apoE all have multiple repeats of 22 amino acids with sequences that suggest amphipathic helices. Tire 391-residue ApoA-IV has 13 tandem 22-residue repeats. Proline and glycine are present in intervening hinge regions.23 This may enable these proteins to spread over and penetrate the surfaces of the lipoprotein micelles. Most of these proteins are encoded by a related multigene family.7 303... 

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... 

Lipoproteins are globular, micelle-like particles consisting of a hydrophobic core of triacylglycerols and cholesterol esters surrounded by an amphipathic coat of protein, phospholipid and cholesterol. The apolipoproteins (apoproteins) on the surface of the lipoproteins help to solubilize the lipids and target the lipoproteins to the correct tissues. There are five different types of lipoprotein, classified according to their functional and physical properties chylomicrons, very low density lipoproteins (VLDLs), intermediate density lipoproteins (IDLs), low density lipoproteins (LDLs), and high density lipoproteins (HDLs). The major function of lipoproteins is to transport triacylglycerols, cholesterol and phospholipids around the body. 

The primary amino acid sequence of apoA-I has been published by Brewer and colleagues (B43) and, with a few minor differences, by Baker et al. (Bl). As with other apolipoproteins that have been sequenced, there are no long sequences of hydrophobic or hydrophilic amino acids, but there is evidence that amphipathic regions of a-helices are formed during combination with lipid, with one face of each helical region more hydrophobic than its opposite face (07). 

Cultivated skin fibroblasts from Tangier patients fail to efflux cholesterol, phosphatidylcholine, or sphingomyelin to exogenous lipid-free apolipoproteins or artificial amphipathic... 

Two important hypotheses which describe interactions between proteins and hydrophobic systems are the fluid mosaic model for membrane structure proposed by Singer and Nicholson (60) and the amphipathic apolipoprotein structure proposed by Segreste/ al. (56). In Singer s model for membrane structure shown in Fig. 1, it is proposed that membrane proteins float in a sea of lipid. The nonpolar regions of the protein are in contact with the nonpolar lipids present in the membrane, whereas the polar surface is exposed to the aqueous environment. 

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 crystal structure of L. migratoria apoLp-III was obtained for the protein in its lipid-free state. The lipid-bound structure of apoLp-III, however, is more interesting since it represents the active form of the protein. To date, no detailed structural reports for exchangeable apolipoproteins in complex with lipid have been reported. The crystal structure of lipid-free apoLp-III demonstrated that the five amphipathic helices orient in such a way that their hydrophobic faces are directed toward each other to form a hydrophobic core while the hydrophilic faces of the helices are exposed to solvent. It has been hypothesized that, upon binding to a... 

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). 

THE AMPHIPATHIC a HELIX A MULTIFUNCTIONAL STRUCTURAL MOTIF IN PLASMA APOLIPOPROTEINS... 

Proteins associated with lipoproteins are referred to as apolipoproteins (abbreviated apo ). Apolipoproteins are amphipathic in nature in that they have both hydrophobic and hydrophilic regions, and can therefore interact both with the lipids of the lipoprotein and with the aqueous environment. Because of the nature of these amphipathic regions, termed amphipathic a helices, they act as protein detergents and have a... 

In order to develop a comparison database with which to analyze the amphipathic helices of the apolipoproteins, we used COMBO, COMNET, and CONSENSUS to analyze five of the seven originally described classes of amphipathic helices (Fig. 4). Classes A, L, and H are included because these three represent surface-active amphipathic helices with measurable lipid affinity. 

Furthermore, as will be described later, a direct comparison of the properties of these two groups with those of class A has enabled us to hypothesize and identify many hitherto unknown properties of apolipoproteins and other class A amphipathic helical peptide analogs. Class M is included because it has significant lipid affinity (although it is not surface active), and class G is included because it is similar to certain types of nonclass A amphipathic helices also found in apolipoproteins. 

Class L (lytic) amphipathic helices include venoms such as bombolitins and mastoparan from Hymenoptera that are hemolytic (Argiolas and Pisano, 1983) antibiotics such as magainins, isolated from Xenopus laevis skin (Zasloff et al., 1988) and seminal plasmin from semen (Sitaram and Nagaraj, 1989). As the name implies, these peptides disrupt artificial phospholipid bilayers, although magainin and seminal plasmin are not hemolytic. Unlike the apolipoproteins and peptide hormones (class H), each peptide of this class consists entirely of an amphipathic helix. 

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