Apolipoproteins exchangeable

It should also be remembered that plasma lipoproteins are constantly in a state of metabolic flux. Some large particles are converted to smaller particles, and vice versa. Lipids and most apolipoproteins exchange or are transferred between particles and particles are released into and removed from the circulation. 

Two apolipoprotein exchange processes between lipoproteins must be considered ... 

After the synthesis and release of chylomicrons into the lymphatic circulation, various exchange processes occur by which apolipoproteins, as well as enzymes and other proteins, may be added or removed. These very complex and incompletely under-... 

With one exception, all apolipoproteins appear to exchange between plasma lipoproteins. The exception is apoB, an apolipoprotein that is present in all chylomicrons and VLDL, LDL, and Lp(a) particles, and which seems to be structurally essential to the integrity of these particles. It appears likely... 

Apolipoprotein B is the major protein component of LDL, and it appears to be an essential component of chylomicrons, VLDL, and LDL. Unlike other apolipoproteins, apoB is insoluble in aqueous buffers after delipidation with organic solvents, and it does not exchange between lipoprotein particles. This may be because of its molecular weight and insolubility it is by far the largest of the apolipoproteins, although, as noted in Section 4.4.1, estimates of molecular weight vary. 

W15. Wilson, D. B., Ellsworth, J. L., and Jackson, R. L., Net transfer of phosphatidylcholine from plasma low density lipoproteins to sphingomyelin-apolipoprotein A-II complexes by bovine liver and human plasma phospholipid exchange proteins. Biochim. Biophys. Acta 620, 550-561 (1980). 

Multidimensional NMR Studies of an Exchangeable Apolipoprotein and Its Interactions with Lipids... 

Exchangeable apolipoproteins are a class of functionally important proteins which play a key role in plasma lipoprotein metabolism. In this capacity they have been associated with several human disorders, including hyperlipidemia and cardiovascular disease (1,2). Apolipophorin-III (apoLp-III) is a model exchangeable apolipoprotein derived from the insect Manr/Mca sexta (166 residues, Mr 18,380). ApoLp-III is a major hemolymph protein in the adult life stage and... 

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... 

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

Fig. 5. Structural relevance of 1 l-mer/22-mer tandem repeats in the exchangeable apolipoproteins. WHEEL/SNORKEL analysis of a 22-mer formed from a tandem repeat of the 11-mer class A amphipathic helix sequence, ELLEALKAKLA. The thin arrows indicate the angle (20°) between tandem repeated residues within the 22-mer (e.g., residue 1 to residue 12) the thick arrows indicate the angle (40°) between tandem repeated residues between two successive 22-mers (e.g., residue I to residue 23).

Diagrammatic representations of the results of the computer-based analysis of the amphipathic helical domains in the exchangeable apolipoproteins are shown in Fig. 7. To facilitate comparison. Fig. 7 also includes information on the location of lipid-associating and non-lipidassociating domains. Based on the properdes of their class A amphipathic helices, the exchangeable apolipoproteins fall into three separate groups apoA-11, apoC-I, apoC-lI, and apoC-Ill, with well-defined class A amphipathic helical domains defined as class A2 domains apoA-I and apoE,... 

Table III is a compilation of physical and chemical properties derived from COMBO analyses of the different sets of potential amphipathic helical classes from all exchangeable apolipoproteins. Two of these physical and chemical properties distinguish the class A2 amphipathic helices from the rest (1) both the mean hydrophobic moment ((/ih)) and the...

Fig. 9. Analysis of the potential amphipathic helices in the exchangeable apolipoproteins by the COMBO/QUALITY and COMBO/QUALITY/SNORKEL programs. The following sequences were analyzed class A2, apoA-II[7-30,39—50,51—71], apoC-I[7-32, 33-53], apoC-II[l4-39, 44-55], apoC-IIl[40-67] class A, apoA-I[44-65, 66-87, 121-142, 143-164, 165-186, 187-208], apoE[161-182, 203-266] class G , apoA-I(8-33], apoA-lV]7-31], apoE[25-5l, 52-83, 91-116, 135-160, 268-285], apoC-lI[60-76], apoC-III[8-29] class Y, apoA-l[88-98, 99-120, 209-219, 220-241], apoA-lV[40-61, 62-94, 139-160, 183-204, 227-248, 249-288, 289-310, 311-332]. COMBO/ QUALITY/SNORKEL is the sum of multiple WHEEL/SNORKEL analyses. (A) COMBO/ QU ALITY/SNORKEL analysis for class A2 (B) COMBO/QUALITY analysis for class A2 (C) COMBO/QUALITY/SNORKEL analysis for class A, (D) COMBO/QUALITY analysis for class G (E) COMBO/QUALITY/SNORKEL analysis for class Y.

The class A amphipathic helical domains present in apoA-IV are unique in their properties. Only four potential class A amphipathic helical domains have been identified in apoA-IV these are rather atypical compared to class A domains in the other exchangeable apolipoproteins (Segrest el a/., 1992). 

A total of nine class G amphipathic helical domains are located in five of the seven exchangeable apolipoproteins, five in apoE and one each in apoA-I, apoA-IV, apoC-II, and apoC-III (Fig. 7). Four of these five domains in apoE are located in the amino-terminal half of the molecule... 

The class Y motif is seen in exchangeable apolipoproteins apoA-I and apoA-IV—8 of the 13 putative amphipathic helical domains in apoA-IV and 4 of the 11 domains in apoA-I are of the Y class. Figures 9E and lOD... 

Helix Length. One property of exchangeable apolipoproteins that must be explained is their ability to target specific lipoprotein particles e.g., apoA-I associates almost entirely with HDLs, which have a smaller radius of curvature than other lipoproteins. ApoE associates invariably... 

As previously noted, apoA-I contains Pro-punctuated tandem repetitive amphipathic helical domains. In apoE, however, the major lipidbinding domain maps to a class A amphipathic helix motif (residues 202-266 see Fig. 7) with no Pro punctuations (Fig. 12A). Thus, this is by far the longest unbroken amphipathic helix among the exchangeable apolipoproteins (65 residues) and one in which the polar-nonpolar interface is in register throughout its length due to a four-amino-acid deletion compared with apoA-I. 

One of the prerequisites for the determination of structure of a protein or a peptide by the X-ray method is that they be crystallized. Because of the amphipathic helical nature of apolipoprotein sequences, these proteins are not easily crystallized. Progress has therefore been impeded in determining the three-dimensional structure of exchangeable apolipoproteins. The first apolipoprotein from insects, apolipophorin, or apoLp-III, has been crystallized and X-ray structure has been described at 2.5 A resolution (Breiter et ai, 1991). 

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