Interfacial properties of amphipathic β strand consensus peptides of apolipoprotein B at oil/water interfaces

Abstract

Apolipoprotein B (apoB) plays an obligate part in the process of the assembly and secretion of nascent VLDLs from the liver and of nascent chylomicrons from intestinal epithelial cells. It participates in the assembly of lipids, including phosphatidylcholine (PC), triacylglycerol (TAG), and probably cholesteryl esters and free cholesterol, into a nascent particle that is then secreted into the extracellular space and ultimately enters the blood. Once in blood plasma, nascent VLDLs are acted on by lipoprotein lipase (1) and converted to intermediate density lipoproteins, which are partly taken up by the liver and partly further converted by hepatic lipase into LDLs (2) after most of the TAG is removed. LDL then circulates in the plasma to be taken up by various organs that require it for the formation of hormones, bile acids, and new cellular membranous components. Excessive LDL accelerates the formation of atherosclerosis and its sequelae. Dietary fat enters the circulation through the formation and secretion of chylomicrons in the intestine. In the capillaries of adipose tissue and muscle, chylomicrons are acted on by lipoprotein lipase, which hydrolyzes much of their TAG and rapidly converts them to chylomicron core remnants. These remnants, enriched in apoE, are taken up rapidly by the liver and their contents recycled into the hepatic pool of lipids. During secretion and after the nascent particles enter the plasma, different soluble, exchangeable apolipoproteins bind to the surfaces and act as cofactors for a number of enzymes, including lipoprotein lipase, hepatic lipase, and LCAT. These small apolipoproteins are able to exchange off of chylomicrons and VLDL as the lipoprotein changes its size, composition, and surface pressure during lipolysis (1). However, apoB-100 and apoB-48 remain bound to the core part of the original nascent particle, which ends up as either chylomicron core remnants or LDLs and does not exchange between particles. In a recent review, Segrest and coworkers (3) suggested that apoB is not exchangeable because tightly bound regions of amphipathic ␤ sheet prevent it coming off of VLDL during metabolism. This paper looks at a consensus sequence derived from the first ␤ sheet region of apoB between apoB-21 and apoB-41 and its interaction with hydrocarAbbreviations: A ␤ S, amphipathic ␤ strand; apoB, apolipoprotein B; A/W, air/water; CSP, consensus sequence peptide, an amphipathic ␣ helix consensus peptide derived from the water-soluble human apolipoproteins apoA-I, apoA-IV, and apoE and with the sequence (PLAEELRARLRAQLEELRERLG)2-NH 2 ; DD/W, dodecane/water; GIXD, grazing incidence X-ray diffraction, HFIP, 1,1,1,3,3,3-hexafluoro-2-propanol; MTP, microsomal triglyceride transfer protein; PC, phosphatidylcholine; TAG, triacylglycerol; TO/W, triolein/water.

Apolipoprotein B is conformationally flexible but anchored at a triolein/water interface: A possible model for lipoprotein surfaces

“…Further, they couldn't be pushed off the surface when the pressure was raised, and they were completely elastic at the interface. We have suggested that these A␤Ss are the anchors that keep apoB bound to the surface (36). However, an A␣H modeling some of the helical parts of apoB (as well as exchangeable apolipoproteins) was forced off the TO͞W surface above an interfacial pressure of Ϸ16 mN͞m.…”

Surface Tensiometry of Apolipoprotein B Domains at Lipid Interfaces Suggests a New Model for the Initial Steps in Triglyceride-rich Lipoprotein Assembly

“…Amphipathic ␤-strands of the C-sheet have a higher affinity for a triolein/water interface than amphipathic ␣-helices and exert more surface pressure both when adsorbed and expanded (6,24). The C-sheet binds irreversibly to a triolein/water interface and cannot be pushed off the droplet surface by compression.…”

“…Amphipathic ␣-helices and amphipathic ␤-strands have different properties at a lipid interface (6,24). The helices exchange on and off a hydrophobic interface and behave viscoelastically.…”

“…Chylomicrons and very low density lipoprotein (VLDL), collectively known as triglyceride-rich lipoproteins (TRLs), 6 distribute triacylglycerides (TAGs) to peripheral tissues for utilization or storage. The remaining particle remnants are smaller, more dense, and enriched in cholesterol esters.…”

“…The ␤1 and ␤2 domains are composed of a series of amphipathic ␤-strands that were proposed to bind directly to a lipoprotein surface and act as an anchor for the protein (4). Amphipathic ␤-strands are formed from a sequence of alternating hydrophobic-hydrophilic amino acids that associate to form a sheet where one side is hydrophilic and the other side is lipophilic (6). The ␣2 and ␣3 domains of apoB are predicted to form amphipathic ␣-helices.…”