The charge and structural stability of apolipoprotein A-I in discoidal and spherical recombinant high density lipoprotein particles.

Sparks, Daniel L.; Lund‐Katz, Sissel; Phillips, Michael C.

doi:10.1016/s0021-9258(18)35686-2

Cited by 165 publications

(97 citation statements)

References 42 publications

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“…However, while the midpoint of denaturation increased significantly, isothermal denaturation analyses suggested that the thermodynamic stability of apoA-I was actually reduced in the presence of TG. This discrepancy between D 1/2 and ⌬G D Њ values is consistent with previous observations and highlights the importance of differentiating between guanidine accessibility and protein stability (10,16,17). This analysis actually appeared to corroborate our finding that the TG-enriched LpA-I showed an increased propensity to allow for apoA-I dissociation after storage at 4ЊC or nondenaturing electrophoresis.…”

Section: Effect Of Dg On Apoa-i Secondary Structure and Stabilitysupporting

confidence: 92%

“…The inclusion of DG molecules only into the LpA-I complex had little effect on the D 1/2 for apoA-I. While the in- creased D 1/2 suggests that the apoA-I molecule is more stable in the presence of TG, analysis of the denaturation curves with the binding model of Aune and Tanford suggests that this is actually not the case (17). Analysis of LpA-I denaturation curves shows that the free energy of stability ( ⌬ G D Њ ) of apoA-I is actually slightly decreased in the presence of TG (Table 2).…”

Section: Effect Of Lpa-i Dg Content On Secondary Structure and Stability Of Apoa-imentioning

confidence: 91%

“…The size and homogeneity of apoA-I complexes were estimated by nondenaturing gradient gel electrophoresis (GGE) on precast 8-25% acrylamide gels (Phastgel; Pharmacia, Uppsala, Sweden) (17). Total glycerides and POPC concentrations were determined enzymatically with kits from Roche Diagnostics (In-dianapolis, IN).…”

Section: Determination Of Lpa-i Physical Characteristicsmentioning

confidence: 99%

“…The effect of guanidine hydrochloride concentration on the secondar y structure of apoA-I in various LpA-I complexes was monitored by the changes in molar ellipticity at 222 nm. Aliquots of each complex (33 g of protein per ml of buffer) were incubated with 0 -6 M guanidine hydrochloride in PBS for 72 h at 4 Њ C. The midpoint of denaturation and free energy of unfolding of apoA-I on the surface of LpA-I complexes was calculated as described previously (17). Experiments were performed on three different LpA-I preparations.…”

Section: Circular Dichroismmentioning

confidence: 99%

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Effect of acylglyceride content on the structure and function of reconstituted high density lipoprotein particles

Braschi

Coffill²,

Neville

et al. 2001

Journal of Lipid Research

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The effects of different acylglycerides on the conformation and charge of apolipoprotein A-I (apoA-I) have been investigated in reconstituted high density lipoproteins (LpA-I). Various amounts of diacylglycerol (DG) and triacylglycerol (TG) were incorporated into sonicated spherical LpA-I particles containing 2 molecules of apoA-I and 80 molecules of phospholipid. Inclusion of 30 molecules of TG into the LpA-I particle increases the net negative charge of apoA-I ( ؊ 8.5 to ؊ 9.3 mV), but has little effect on the amount and thermodynamic stability of the ␣ helices in apoA-I. Incorporation of 30 molecules of DG into the lipoprotein complex promotes a small increase in the ␣ -helix content and stability, but greatly increases the net negative charge of apoA-I ( ؊ 8.5 to ؊ 11.2 mV). Inclusion of DG increases the immunoreactivity of two epitopes in the N terminus of apoA-I, but decreases the exposure of a domain closer to the C terminus (residues 148-186) of the apoprotein. In contrast, TG increases the exposure of epitopes over the entire apoA-I molecule; TG increases the immunoreactivity of epitopes for 13 different monoclonal antibodies to apoA-I. Incubations with purified lecithin:cholesterol acyltransferase show that cholesterol esterification is stimulated by DG, but inhibited by TG. The data show that TG and DG have different effects on apoA-I structure and function and this suggests that the TG-to-DG ratio in HDL may directly affect the metabolism of this lipoprotein class. -Braschi, S.

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Section: Effect Of Dg On Apoa-i Secondary Structure and Stabilitysupporting

confidence: 92%

Section: Effect Of Lpa-i Dg Content On Secondary Structure and Stability Of Apoa-imentioning

confidence: 91%

Section: Determination Of Lpa-i Physical Characteristicsmentioning

confidence: 99%

Section: Circular Dichroismmentioning

confidence: 99%

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Effect of acylglyceride content on the structure and function of reconstituted high density lipoprotein particles

Braschi

Coffill²,

Neville

et al. 2001

Journal of Lipid Research

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“…In addition, phospholipid acyl-chain and head group packing is more ordered in spherical (A-I)rHDL than in discoidal (A-I)rHDL (16,38). There are also differences in the ␣-helical content of apoA-I in spherical and discoidal (A-I)rHDL and in the microenvironment around the lysine residues on apoA-I in these particles (39,40). Precisely how these structural differences between apoA-I in spherical and discoidal HDL relate to their relative abilities to inhibit VCAM-1 expression remains to be determined.…”

Section: Discussionmentioning

confidence: 97%

Ability of reconstituted high density lipoproteins to inhibit cytokine-induced expression of vascular cell adhesion molecule-1 in human umbilical vein endothelial cells

Baker

Rye

Gamble

et al. 1999

Journal of Lipid Research

134

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Previous studies have shown that both high density lipoproteins (HDL) isolated from human plasma and reconstituted HDL (rHDL) are effective inhibitors of adhesion molecule expression in human endothelial cells. In this study rHDL have been used to investigate whether HDL particle shape, size, apolipoprotein composition or lipid composition are important determinants of the ability of HDL to inhibit the TNF-␣ induced expression of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs). On the basis of these studies it is possible to draw several firm conclusions. i ) Neither phospholipid-containing vesicles nor lipid-free apolipoprotein (apo) A-I inhibit VCAM-1 expression in HUVECs. ii ) Simple discoidal complexes containing only phospholipid and apoA-I (discoidal (A-I)rHDL) are sufficient to inhibit the TNF-␣ -induced expression of VCAM-1 in HUVECs. iii ) Spherical apoA-I-containing rHDL (spherical (A-I)rHDL) are superior to discoidal (A-I)rHDL as inhibitors. iv ) The particle size of spherical (A-I)rHDL has no influence on the inhibition. v ) Spherical rHDL that contain apoA-I are superior as inhibitors of VCAM-1 to those containing apoA-II when the rHDL preparations are equated for apolipoprotein molarity. However, when compared at equivalent particle molarities, this difference is no longer apparent. vi ) Replacement of cholesteryl esters with triglyceride in the core of spherical (A-I)rHDL has no effect on the ability of these particles to inhibit VCAM-1 expression.From these results it is tempting to speculate that variations in inhibitory activity may contribute to the variations observed in the anti-atherogenicity of different HDL subpopulations.-

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Phosphatidylethanolamine accelerates aggregation of the amyloidogenic N‐terminal fragment of apoA‐I

et al. 2020

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Membrane lipid composition is known to influence aggregation and fibril formation of many amyloidogenic proteins. Here, we found that phosphatidylethanolamine (PE) accelerates aggregation of the N-terminal 1-83 fragment of an amyloidogenic G26R variant of apoA-I on lipid membranes. Circular dichroism and isothermal titration calorimetry measurements demonstrated that PE does not affect the α-helical structure and lipid binding property of apoA-I 1-83/G26R. Rather, fluorescence measurements indicated that PE induces more ordered lipid packing at the interfacial and acyl chain regions, providing more hydrophobic environments especially around the highly amyloidogenic regions in apoA-I on the membrane surface. These results suggest that PE promotes aggregation of the amyloidogenic N-terminal fragment of apoA-I on lipid membranes by inducing hydrophobic membrane environments.

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The charge and structural stability of apolipoprotein A-I in discoidal and spherical recombinant high density lipoprotein particles.

Cited by 165 publications

References 42 publications

Effect of acylglyceride content on the structure and function of reconstituted high density lipoprotein particles

Effect of acylglyceride content on the structure and function of reconstituted high density lipoprotein particles

Ability of reconstituted high density lipoproteins to inhibit cytokine-induced expression of vascular cell adhesion molecule-1 in human umbilical vein endothelial cells

Phosphatidylethanolamine accelerates aggregation of the amyloidogenic N‐terminal fragment of apoA‐I

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