Role of the stereochemistry of the hydroxyl group of cholesterol and the formation of nonbilayer structures in phosphatidylethanolamines

Cheetham, James J.; Wachtel, Ellen; Bach, D.; Epand, Richard M.

doi:10.1021/bi00448a036

Cited by 75 publications

(66 citation statements)

References 41 publications

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“…At low concentrations (up to around 15-20% of the total membrane lipids), CHO favored the binding of G␣ proteins to lipid bilayers, but at higher concentrations (30-50 mol% CHO) it impaired this binding. The ability of this lipid to induce nonlamellar structures at low mol fractions (less than 0.2) and inhibit them at higher mol fractions would explain the biphasic behavior of the G␣i binding to CHO-containing membranes (25). On the other hand, CHO intercalates in the surface of the lipid leaflet, a potential target for the binding of the G protein fatty acid moiety, which favors the interaction between G proteins and membranes (26,27).…”

Section: Discussionmentioning

confidence: 99%

Role of lipid polymorphism in G protein-membrane interactions: Nonlamellar-prone phospholipids and peripheral protein binding to membranes

Escribá

Ozaita

Ribas

et al. 1997

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

106

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Heterotrimeric G proteins (peripheral proteins) conduct signals from membrane receptors (integral proteins) to regulatory proteins localized to various cellular compartments. They are in excess over any G protein-coupled receptor type on the cell membrane, which is necessary for signal amplification. These facts account for the large number of G protein molecules bound to membrane lipids. Thus, the protein-lipid interactions are crucial for their cellular localization, and consequently for signal transduction. In this work, the binding of G protein subunits to model membranes (liposomes), formed with defined membrane lipids, has been studied. It is shown that although G protein ␣-subunits were able to bind to lipid bilayers, the presence of nonlamellarprone phospholipids (phosphatidylethanolamines) enhanced their binding to model membranes. This mechanism also appears to be used by other (structurally and functionally unrelated) peripheral proteins, such as protein kinase C and the insect protein apolipophorin III, indicating that it could constitute a general mode of protein-lipid interactions, relevant in the activity and translocation of some peripheral (amphitropic) proteins from soluble to particulate compartments. Other factors, such as the presence of cholesterol or the vesicle surface charge, also modulated the binding of the G protein subunits to lipid bilayers. Conversely, the binding of G protein-coupled receptor kinase 2 and the G protein ␤-subunit to liposomes was not increased by hexagonally prone lipids. Their distinct interactions with membrane lipids may, in part, explain the different cellular localizations of all of these proteins during the signaling process.

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Section: Discussionmentioning

confidence: 99%

Role of lipid polymorphism in G protein-membrane interactions: Nonlamellar-prone phospholipids and peripheral protein binding to membranes

Escribá

Ozaita

Ribas

et al. 1997

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

106

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“…It was observed that the enantiomer of cholesterol ( ent -cholesterol) could restore ligand binding and receptor signaling after cholesterol-depletion, whereas the diastereomer ( epi -cholesterol) did not (Jafurulla et al, 2014). Epi -cholesterol was shown before to have different biophysical effects on the bilayer due to different tilt angles and phase transition characteristics (Cheetham et al, 1989). The ligand-independent oligomerization of serotonin 5-HT 1 A receptors in living cells was observed with FRET and appeared to be enhanced upon acute cholesterol depletion (Paila et al, 2011).…”

Section: Specific Membrane Components Influence Gpcr Oligomerizatimentioning

confidence: 99%

Membrane-Mediated Oligomerization of G Protein Coupled Receptors and Its Implications for GPCR Function

2016

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The dimerization or even oligomerization of G protein coupled receptors (GPCRs) causes ongoing, controversial debates about its functional role and the coupled biophysical, biochemical or biomedical implications. A continously growing number of studies hints to a relation between oligomerization and function of GPCRs and strengthens the assumption that receptor assembly plays a key role in the regulation of protein function. Additionally, progress in the structural analysis of GPCR-G protein and GPCR-ligand interactions allows to distinguish between actively functional and non-signaling complexes. Recent findings further suggest that the surrounding membrane, i.e., its lipid composition may modulate the preferred dimerization interface and as a result the abundance of distinct dimeric conformations. In this review, the association of GPCRs and the role of the membrane in oligomerization will be discussed. An overview of the different reported oligomeric interfaces is provided and their capability for signaling discussed. The currently available data is summarized with regard to the formation of GPCR oligomers, their structures and dependency on the membrane microenvironment as well as the coupling of oligomerization to receptor function.

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“…While ent -cholesterol shares identical physicochemical properties with cholesterol, previous studies have shown that the biophysical properties of epi -cholesterol and native cholesterol are different (Westover and Covey, 2004; Covey, 2009). epi -Cholesterol has been reported to differ in its tilt angles, condensing ability, and phase transition properties from cholesterol in membranes (Demel et al, 1972; Dufourc et al, 1984; Murari et al, 1986; Cheetham et al, 1989). We show here that cholesterol and ent -cholesterol share comparable ability in increasing membrane dipole potential.…”

Section: Introductionmentioning

confidence: 99%

Membrane dipole potential is sensitive to cholesterol stereospecificity: Implications for receptor function

Bandari

Chakraborty

Covey³

et al. 2014

Chemistry and Physics of Lipids

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Dipole potential is the potential difference within the membrane bilayer, which originates due to the nonrandom arrangement of lipid dipoles and water molecules at the membrane interface. Cholesterol, an essential lipid in higher eukaryotic membranes, has previously been shown to increase membrane dipole potential. In this work, we explored the effect of stereoisomers of cholesterol, ent-cholesterol and epi-cholesterol, on membrane dipole potential, monitored by the dual wavelength ratiometric approach utilizing the probe di-8-ANEPPS. Our results show that cholesterol and ent-cholesterol share comparable ability in increasing membrane dipole potential. In contrast, epi-cholesterol displays a slight reduction in membrane dipole potential. Our results constitute the first report on the effect of stereoisomers of cholesterol on membrane dipole potential, and imply that an extremely subtle change in sterol structure can significantly alter the dipolar field at the membrane interface. These results assume relevance in the context of differential abilities of these stereoisomers of cholesterol in supporting the activity of the serotonin1A receptor, a representative G protein-coupled receptor. The close correlation between membrane dipole potential and receptor activity provides new insight in receptor-cholesterol interaction in terms of stereospecificity. We envision that membrane dipole potential could prove to be a sensitive indicator of lipid-protein interactions in biological membranes.

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Role of the stereochemistry of the hydroxyl group of cholesterol and the formation of nonbilayer structures in phosphatidylethanolamines

Cited by 75 publications

References 41 publications

Role of lipid polymorphism in G protein-membrane interactions: Nonlamellar-prone phospholipids and peripheral protein binding to membranes

Role of lipid polymorphism in G protein-membrane interactions: Nonlamellar-prone phospholipids and peripheral protein binding to membranes

Membrane-Mediated Oligomerization of G Protein Coupled Receptors and Its Implications for GPCR Function

Membrane dipole potential is sensitive to cholesterol stereospecificity: Implications for receptor function

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