Dissociation of Apolipoprotein AI from Apoprotein‐Lipid Complexes and from High‐Density Lipoproteins

Rosseneu, Maryvonne; Tornout, Philippe Van; Lievens, Marie-José; Schmitz, Gerd; Assmann, Gerd

doi:10.1111/j.1432-1033.1982.tb06986.x

Cited by 15 publications

(6 citation statements)

References 18 publications

(14 reference statements)

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“…Similarly, guanidinium hydrochloride (GdmHCl) denaturation studies of mature spherical HDL from human plasma revealed that fusion and rupture are the two main kinetic events in HDL disruption, and showed that these events are associated with high free energy barriers that determine HDL stability [∆G* ) 16-17 kcal/mol (17)]. These results corroborate the earlier observations of the heator denaturant-induced HDL enlargement and disruption (23,24) and explain the slow unfolding of HDL proteins by GdmHCl (23,25,26). They indicate clearly that the kinetic stability of HDL originates from the high-energy transition states that form the bottlenecks of the fusion and rupture reactions.…”

supporting

confidence: 83%

Poly(ethylene glycol)-Induced Fusion and Destabilization of Human Plasma High-Density Lipoproteins

2004

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High-density lipoproteins (HDL) are macromolecular complexes of specific proteins and lipids that mediate the removal of cholesterol from peripheral tissues. Chemical unfolding revealed that HDL fusion and rupture are the two main kinetic steps in HDL denaturation. Here we test the hypothesis that lipid fusogens such as poly(ethylene glycol) (PEG) may promote lipoprotein fusion and rupture and thereby destabilize HDL. We analyze thermal disruption of spherical HDL in 0-15% PEG-8000 by calorimetric, spectroscopic, electron microscopic, and light scattering techniques. We demonstrate that the two irreversible high-temperature endothermic HDL transitions involve particle enlargement and show a heating rate dependence characteristic of kinetically controlled reactions with high activation energy. The first calorimetric transition reflects HDL fusion and dissociation of lipid-poor apolipoprotein A-1 (apoA-1), and the second transition reflects HDL rupture and release of the apolar lipid core. Neither transition involves substantial protein unfolding; thus, the transition heat originates from lipid and/or protein dissociation and repacking. At room temperature, PEG-8000 induces HDL fusion that is distinct from the heat-, denaturant-, or enzyme-induced fusion since it leads to formation of larger particles and does not involve apoA-1 dissociation. Increasing the PEG concentration in solution from 0 to 15% leads to low-temperature shifts by approximately -18 degrees C in the two calorimetric HDL transitions without altering their nature. Thus, consistent with our hypothesis, PEG-8000 induces fusion and reduces the thermal stability of HDL. Our results suggest that PEG is useful for the analysis of the molecular events involved in metabolic HDL remodeling and fusion.

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supporting

confidence: 83%

Poly(ethylene glycol)-Induced Fusion and Destabilization of Human Plasma High-Density Lipoproteins

2004

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“…Dose-Dependent Effects of CP on HDL Size and Release of Apo A-I. Previous studies showed that relative to free apos, apos within HDL are more stable and require higher concentrations of chaotropic agents for unfolding ( − ). Using SEC, we compared the effects of various doses of Gdm-Cl on HDL.…”

Section: Resultsmentioning

confidence: 99%

“…CP of human HDL transfers apo A-I to water with the concomitant formation of a HDL-like particle ( − ). As reviewed by Gursky, HDL is stabilized by kinetic factors.…”

Section: Discussionmentioning

confidence: 99%

Speciation of Human Plasma High-Density Lipoprotein (HDL): HDL Stability and Apolipoprotein A-I Partitioning

et al. 2007

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The distribution of apolipoprotein (apo) A-I between human high-density lipoproteins (HDL) and water is an important component of reverse cholesterol transport and the atheroprotective effects of HDL. Chaotropic perturbation (CP) with guanidinium chloride (Gdm-Cl) reveals HDL instability by inducing the unfolding and transfer of apo A-I but not apo A-II into the aqueous phase while forming larger apo A-I deficient HDL-like particles and small amounts of cholesteryl ester-rich microemulsions (CERMs). Our kinetic and hydrodynamic studies of the CP of HDL species separated according to size and density show that (1) CP mediated an increase in HDL size, which involves quasi-fusion of surface and core lipids, and release of lipid-free apo A-I (these processes correlate linearly), (2) >94% of the HDL lipids remain with an apo A-I deficient particle, (3) apo A-II remains associated with a very stable HDL-like particle even at high levels of Gdm-Cl, and (4) apo A-I unfolding and transfer from HDL to water vary among HDL subfractions with the larger and more buoyant species exhibiting greater stability. Our data indicate that apo A-I's on small HDL (HDL-S) are highly dynamic and, relative to apo A-I on the larger more mature HDL, partition more readily into the aqueous phase, where they initiate the formation of new HDL species. Our data suggest that the greater instability of HDL-S generates free apo A-I and an apo A-I deficient HDL-S that readily fuses with the more stable HDL-L. Thus, the presence of HDL-L drives the CP remodeling of HDL to an equilibrium with even larger HDL-L and more lipid-free apo A-I than with either HDL-L or HDL-S alone. Moreover, according to dilution studies of HDL in 3 M Gdm-Cl, CP of HDL fits a model of apo A-I partitioning between HDL phospholipids and water that is controlled by the principal of opposing forces. These findings suggest that the size and relative amount of HDL lipid determine the HDL stability and the fraction of apo A-I that partitions into the aqueous phase where it is destined for interaction with ABCA1 transporters, thereby initiating reverse cholesterol transport or, alternatively, renal clearance.

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“…To begin the development of these capabilities, we explore the erasure of apoA-I-induced nanoscale confinement of the lipid bilayer using a chemical denaturant. It is well-known that interaction between rHDL and concentrated guanidinium hydrochloride (GdmHCl) results in complete denaturation of lipid-associated apoA-I in solution . Incubation of labeled rHDL with 6 M GdmHCl induces protein denaturation, in solution, of DMPC-apoA-I rHDL particles as indicated by the change in tryptophanyl fluorescence (SI).…”

Section: Resultsmentioning

confidence: 99%

Bridging Across Length Scales: Multi-Scale Ordering of Supported Lipid Bilayers via Lipoprotein Self-assembly and Surface Patterning

et al. 2008

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We show that a two-step process, involving spontaneous self-assembly of lipids and apolipoproteins and surface patterning, produces single, supported lipid bilayers over two discrete and independently adjustable length scales. Specifically, an aqueous phase incubation of DMPC vesicles with purified apolipoprotein A-I results in the reconstitution of high density lipoprotein (rHDL), wherein nanoscale clusters of single lipid bilayers are corralled by the protein. Adsorption of these discoidal particles to clean hydrophilic glass (or silicon) followed by direct exposure to a spatial pattern of short-wavelength UV radiation directly produces microscopic patterns of nanostructured bilayers. Alternatively, simple incubation of aqueous phase rHDL with a chemically patterned hydrophilic/hydrophobic surface produces a novel compositional pattern, caused by an increased affinity for adsorption onto hydrophilic regions relative to the surrounding hydrophobic regions. Further, by simple chemical denaturation of the boundary protein, nanoscale compartmentalization can be selectively erased, thus producing patterns of laterally fluid, lipid bilayers structured solely at the mesoscopic length scale. Since these aqueous phase microarrays of nanostructured lipid bilayers allow for membrane proteins to be embedded within single nanoscale bilayer compartments, they present a viable means of generating high-density membrane protein arrays. Such a system would permit in-depth elucidation of membrane protein structure-function relationships and the consequences of membrane compartmentalization on lipid dynamics.

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Dissociation of Apolipoprotein AI from Apoprotein‐Lipid Complexes and from High‐Density Lipoproteins

Cited by 15 publications

References 18 publications

Poly(ethylene glycol)-Induced Fusion and Destabilization of Human Plasma High-Density Lipoproteins

Poly(ethylene glycol)-Induced Fusion and Destabilization of Human Plasma High-Density Lipoproteins

Speciation of Human Plasma High-Density Lipoprotein (HDL): HDL Stability and Apolipoprotein A-I Partitioning

Bridging Across Length Scales: Multi-Scale Ordering of Supported Lipid Bilayers via Lipoprotein Self-assembly and Surface Patterning

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