The self-association of apoA-II, an apoprotein of the human high density lipoprotein complex

Gwynne, John T.; Palumbo, Giuseppe; Osborne, James C.; Brewer, H. Bryan; Edelhoch, Harold

doi:10.1016/0003-9861(75)90111-3

Cited by 56 publications

(59 citation statements)

References 26 publications

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“…Gwynne et al [3] could not demonstrate any effect at 1.8 M GdmCl on the tryptophanyl polarization of HDL though we observed a small but significant decrease of the emission intensity at 335 nm together with a red shift of the maximum towards 336 nm.…”

Section: Discussioncontrasting

confidence: 82%

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

Rosseneu¹,

Tornout²,

Lievens³

et al. 1982

European Journal of Biochemistry

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The dissociation of the apoprotein A1 (apoAI) from the apoAI-dimyristoylglycerophosphocholine complex and from human high-density lipoproteins (HDL), was induced by incubation with guanidinium hydrochloride at concentrations between 0 M and 7 M.The kinetics and extent of denaturation were followed by monitoring both the fluidity of the lipid phase by fluorescence polarization measurements and the protein conformation by measuring the tryptophanyl fluorescence emission.The association with lipids protects apoAI against denaturation both in HDL and in the apoAI-phospholipid complex. The results of the kinetic and end-point measurements suggest that the denaturing effect of guanidine hydrochloride on the apoAI-lipid complex and on HDL is a two-step process. It involves the dissociation of the apoAI-phospholipid bond, as evidenced by fluidity measurements: this effect is maximal between 3 M and 4 M guanidine hydrochloride. The conformational change ofthe apoAI protein into a randomly coiled structure with the tryptophanyl residues exposed to the solvent is maximal between 4 M and 6 M guanidine hydrochloride.HDL and the apoAI-phospholipid complex have a closely similar behaviour towards denaturation by guanidine hydrochloride indicating that the phospholipid-apoAI association in HDL is primarly responsible for the stability of the lipoprotein molecule.Several studies have indicated that the conformation of the human apoAI protein is labile and can be altered by proteinprotein interaction, or lipid-apoprotein association [I]. The protein conformation is also sensitive to temperature [2] and to denaturating agcnts such as guanidinium hydrochloride [3 -51. The lipid-apoAl association can be disrupted by the competition with another apoprotein of higher affinity [6,7], by heat treatment [8] or by exposure to guanidinium hydrochloride [9 -1 I].We have previously studied the kinetics if apoAI-lipid association and characterized the isolated complexes [12 -151.In this paper we report on the dissociation of apoAI from these complexes and from native HDL in an attempt to evaluate the stability of the lipid-apoAI association in relation to the functional metabolic transfer of apoAI and apoAI-lipid complexes between lipoprotein fractions. MATERIALS AND METHODS Lipids und ApoproteinsHigh-density lipoproteins were isolated by ultracentrifugal flotation at densities 1.08 < e < 1.21 g/ml from fresh human plasma [16]. The human apolipoprotein A1 was prepared from the HDL fraction by chromatography on a DEAE-cellulose column in 8 M urea [12]. The purity of the fraction was checked by immunodiffusion using specific antisera againstAbbreoiulions. HDL. high-density lipoproteins; apoAI, apo-protein AI ; GdmHCI, guanidinium hydrochloride. albumin, apoB, apoAII, apoCII, and apoCIII proteins. The dimyristoylglycerophosphocholine (Sigma Co.) vesicles were prepared by sonication [12].Guanidinium hydrochloride ultrapure was purchased from Merck (Darmstadt) and acrylamide from Serva (Heidelberg). The apoAI-phospholipid complex was prepared by m...

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Section: Discussioncontrasting

confidence: 82%

“…The protein conformation is also sensitive to temperature [2] and to denaturating agcnts such as guanidinium hydrochloride [3 -51. The lipid-apoAl association can be disrupted by the competition with another apoprotein of higher affinity [6,7], by heat treatment [8] or by exposure to guanidinium hydrochloride [9 -1 I].…”

mentioning

confidence: 99%

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

Rosseneu¹,

Tornout²,

Lievens³

et al. 1982

European Journal of Biochemistry

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“…Although apoA-I is globular (18) there must be special features in the tertiary structure of the molecule which minimize the stabilizing effects of long-range interactions. A similar interpretation is suggested by the previous finding that at 250 apoA-I is completely denatured in 1.7 M guanidine-HCI (19), whereas concentrations of 6-8 M are required to denature most proteins (20). A relatively loosely folded but helix-containing conformation of apoA-I with a low free energy of stabilization may be important in its function of lipid binding.…”

supporting

confidence: 80%

Apoprotein stability and lipid-protein interactions in human plasma high density lipoproteins.

Tall¹,

Small²,

Shipley³

et al. 1975

Proc. Natl. Acad. Sci. U.S.A.

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Temperature-dependent conformational changes of the principal apoprotein of human plasma high density lipoprotein (HDL), apoA-I, have been studied in the isolated apoprotein, in complexes of apoprotein with phospholipid, and in intact HDL. Differential scanning calorimetry shows that in solution apoA-I undergoes a reversible, twostate thermal denaturation (midpoint temperature 540). The enthalpy (2.4 cal/g) (10.0 J/g) and specific heat change (0.08 cal/°C per g) (0.33 J/°C per g) associated with the denaturation were used to calculate the free energy difference (AG) between native and unfolded apoA-I at 37°. AG (2.4 kcal/ mol) (10.0 kJ/mol) is less than that of other globular proteins (typically 8-14 kcal/mol) (33-59 kJ/mol), indicating that at 370 native apoA-I has a loosely folded conformation. Turbidity studies show that apoA-I is able to solubilize phospholipidin its native but not in its denatured form. Mixtures of apo-HDL (the total apoprotein of HDL) or apoA-I with dimyristoyl lecithin show a thermal transition at about 850 n-ot present in the lecithin or the apoprotein alone, which indicates that the native conformation of the apoprotein is stabilized by phospholipid. Scanning calorimetry of intact HDL shows a high-temperature endotherm associated with disruption of the HDL particle, su esting that in HDL the conformation of apoA-I is also stabilized by interaction with lipid. The loosely folded conformation of native, uncomplexed apoA-I may be specially adapted to the binding of lipid, since this process may involve both hydrophobic sites on the surface of the protein and concealed apolar amino acid residues that are exposed by a cooperative, low energy unfolding process.A knowledge of the structure and thermodynamic stability of serum lipoproteins is important to an understanding of their metabolism and role in diseases such as atherosclerosis. The human plasma high density lipoproteins (HDL) are spherical particles (1, 2) consisting of about 50% protein, 22% phospholipids, 3% free cholesterol, 14% cholesterol esters, and 8% triglycerides (3). The proteins (apo-HDL) include approximately 60-65% apoA-I [molecular weight (Mr) 28,331], 30% apoA-2 (Mr 17,380) and 5-10% low Mr C-peptides (4, 5). The proteins and polar head groups of phospholipids occupy the surface of the lipoprotein particle while the apolar lipid moieties form a hydrophobic core (1, 2). Further, the conformations of the apoproteins of HDL appear to be stabilized by interaction with lipids (3, 4). In the present study, we show that the principal apoprotein of human HDL, apoA-I, undergoes a reversible temperaturedependent conformational change with unusual thermodynamic properties. A comparison with other water-soluble proteins suggests a loosely folded structure of the native apo- Fig. la and b). From the DSC thermogram, it is possible to measure both the calorimetric enthalpy of the transition in cal/g (AHcal) (1 cal = 4.184 J) from the area under the curve, and the effective enthalpy in cal/mol (AHvH) using an expression der...

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“…S4) (67,74). Consistent with this observation, solvent accessibility and Trp fluorescence measurements of monomeric lipid-free apoA-I demonstrate that the tertiary structure folding provides a hydrophobic environment for all four tryptophans (62,74,75). This suggests that tryptophans are directly involved in interhelical interactions within the fourhelix bundle.…”

Section: Discussionsupporting

confidence: 62%

Impact of Self-association on Function of Apolipoprotein A-I

Jayaraman

Abe-Dohmae

Yokoyama

et al. 2011

Journal of Biological Chemistry

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Background: Self-association is an intrinsic property of exchangeable apolipoproteins but an under-explored feature of the major protein of good cholesterol, apolipoprotein A-I. Result: Different degrees of apolipoprotein A-I self-association exhibit distinct in vitro lipid remodeling and cellular lipid release efficiencies. Conclusion: Self-association of apolipoprotein A-I modulates the biogenesis of high density lipoprotein. Significance: This is the first study to demonstrate that self-association of apolipoprotein A-I attunes key steps in reverse cholesterol transport.

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The self-association of apoA-II, an apoprotein of the human high density lipoprotein complex

Cited by 56 publications

References 26 publications

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

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

Apoprotein stability and lipid-protein interactions in human plasma high density lipoproteins.

Impact of Self-association on Function of Apolipoprotein A-I

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