Temperature and Composition Dependence of the Interaction of δ-Lysin with Ternary Mixtures of Sphingomyelin/Cholesterol/POPC

Pokorny, Antje; Yandek, Lindsay E.; Elegbede, Adekunle; Hinderliter, Anne; Almeida, Paulo F.

doi:10.1529/biophysj.106.085027

Cited by 98 publications

(154 citation statements)

References 75 publications

(127 reference statements)

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“…When purifi ed AChR or ␥ M4 was included in different lipid:protein ratios in the reconstituted system, no significant effects were apparent on the lipid composition of DRM and DSM fractions, suggesting that lipid composition is independent of protein content. Recent studies using lipid vesicles having the same composition as in the present study (Chol/SM/POPC) reported the occurrence of ( l d + l o ) domain coexistence ( 70,71 ) or only one type of domain ( 72 ). It is interesting to compare the DRM and DSM lipid compositions obtained from the different liposomes studied ( Fig.…”

Section: Discussionmentioning

confidence: 60%

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Partition profile of the nicotinic acetylcholine receptor in lipid domains upon reconstitution

Bermúdez

Antollini

Nievas

et al. 2010

Journal of Lipid Research

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tains a relatively large extracellular domain and four hydrophobic membrane-spanning segments referred to as M1-M4, ending in a short extracellular carboxyl terminal domain. Three concentric rings can be distinguished in the AChR transmembrane (TM) region ( 1, 2 ): the M2 TM segments of all subunits outline the inner ring and form the walls of the ion channel proper; M1 and M3 constitute the middle ring; and the M4 segments form the outer ring, which is in closest contact with the AChR lipid microenvironment.One outstanding characteristic of the mature neuromuscular junction (NMJ) is the high density of AChR clusters at the postsynaptic membrane ( 3 ). Neural agrin, an extracellular proteoglycan, initiates the cascade of events in the AChR clustering process in the myotubes by fi rst activating MuSK (muscle-specifi c receptor tyrosine kinase), which subsequently induces the activation of several other intracellular enzymes. Finally, association of AChR with rapsyn, a cytoplasmic peripheral membrane protein colocalized with AChR in vivo, mediates binding to the cytoskeleton ( 3, 4 ), leading in turn to effi cient receptor clustering ( 5 ). Lipids have been postulated to be involved in AChR nanodomain organization and clustering, presumably at early, preinnervation stages of development ( 6 ). The plasma membrane organization of living cells is currently considered to be a mosaic of macroscopic and stable or transient and short-scale segregated domains (reviewed by Ref. 7 ). Lipid domains termed lipid "rafts" are highly enriched in both cholesterol (Chol) and sphingolipids.Abstract The nicotinic acetylcholine receptor (AChR) is in intimate contact with the lipids in its native membrane. Here we analyze the possibility that it is the intrinsic properties of the AChR that determine its partition into a given lipid domain. Torpedo AChR or a synthetic peptide corresponding to the AChR ␥ M4 segment (the one in closer contact with lipids) was reconstituted into "raft "-containing model membranes. The distribution of the AChR was assessed by Triton X-100 extraction in combination with fl uorescence studies, and lipid analyses were performed on each sample. The infl uence of rapsyn, a peripheral protein involved in AChR aggregation, was studied. Raft -like domain aggregation was also studied using membranes containing the ganglioside GM1 followed by GM1 crosslinking. The ␥ M4 peptide displays a marked preference for raft -like domains. In contrast, AChR alone or in the presence of rapsyn or ganglioside aggregation exhibits no such preference for raft-like domains, but it does cause a signifi cant reduction in the total amount of these domains. The results indicate that the distribution of the AChR in lipid domains cannot be due exclusively to the intrinsic physicochemical properties of the protein and that there must be an external signal in native cell membranes that directs the AChR to a specifi c membrane domain. The nicotinic acetylcholine receptor (AChR) is a pentameric transmembrane glycoprotein composed of four dif...

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Section: Discussionmentioning

confidence: 60%

“…It is interesting to compare the DRM and DSM lipid compositions obtained from the different liposomes studied ( Fig. 3A ) with the phase diagram postulated by Pokorny et al ( 70 ) ( Fig. 6 ), bearing in mind that detergent extraction at 4°C results in the formation of a quaternary phase system.…”

Section: Discussionmentioning

confidence: 80%

Partition profile of the nicotinic acetylcholine receptor in lipid domains upon reconstitution

Bermúdez

Antollini

Nievas

et al. 2010

Journal of Lipid Research

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“…Our data indicates that apoA-I solubilizes a more homogeneous bilayer which is consistent with the formation of condensed cholesterol/phospholipid complexes whose stoichiometry increases with the cholesterol concentration. However, in the ternary system of phosphatidylcholine/ sphingomyelin/cholesterol, where lateral fluid-fluid phase separation into phospholipid-rich l d and sphingomyelin/cholesterol-rich l o domains has been demonstrated, apoA-I preferentially solubilizes cholesterol-poor l d domains [21,52]. In our model (Step 1), the hydrophobic Cterminal α-helices of apoA-I insert into lattice defects in the membrane surface which occurs when DMPC bilayers undergo a thermal phase transition ( Figure 9).…”

Section: Discussionmentioning

confidence: 99%

Cholesterol is a determinant of the structures of discoidal high density lipoproteins formed by the solubilization of phospholipid membranes by apolipoprotein A-I

Massey

Pownall

2008

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Formation of discoidal high density lipoproteins (rHDL) by apolipoprotein A-I (apoA-I) mediated solubilization of dimyristoyl phosphatidylcholine (DMPC) multilamellar vesicles (MLV) was dramatically affected by bilayer cholesterol concentration. At a low ratio of DMPC/apoA-I (2 mg DMPC/mg apoA-I, 84/1 mol/mol), sterols (cholesterol, lathosterol, and β-sitosterol) that form ordered lipid phases increase the rate of solubilization similarly, yielding rHDL with similar structures. By changing the temperature and sterol concentration, the rates of solubilization varied almost 3 orders of magnitude; however, the sizes of the rHDL were independent of the rate of their formation and dependent upon the bilayer sterol concentration. At a high ratio of DMPC/apoA-I (10/1 mg DMPC/mg apoA-I, 420/1 mol/mol), changing the temperature and cholesterol concentration yielded rHDL that varied greatly in size, phospholipid/protein ratio, mol% cholesterol, and number of apoA-I molecules per particle. rHDL were isolated that had 2, 4, 6, and 8 molecules of apoA-I per particle, mean diameters of 117, 200, 303, and 396 Å, and a mol% cholesterol that was similar to the original MLV. Kinetic studies demonstrated the different sized rHDL are formed independently and concurrently. The rate of formation, lipid composition, and three-dimensional structures of cholesterol-rich rHDL are dictated primarily by the original membrane phase properties and cholesterol content. The size speciation of rHDL and probably nascent HDL formed via the activity of the ABCA1 lipid transporter are mechanistically linked to the cholesterol content of the membranes from which they were formed.

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“…Thus, membranes composed of POPC, which forms zwitterionic bilayers with liquid disordered phase properties at 25°C, along with model membranes of increased complexity, including POPC/POPG (80:20 molar ratio) and POPC/Chol/SM (27:33:40), were included. At 25°C, POPC/Chol/SM (27:33:40) membranes are in a homogeneous liquid-ordered phase (42). Phospholipids with a PG headgroup are negatively charged and were included to evaluate the effects of charge.…”

Section: Cyclotide-membrane Binding Affinity Is Dependent On Lipidmentioning

confidence: 99%

Phosphatidylethanolamine Binding Is a Conserved Feature of Cyclotide-Membrane Interactions

Henriques

Huang

Castanho

et al. 2012

Journal of Biological Chemistry

121

208

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Background: Cyclotides are a family of plant-expressed pesticidal cyclic peptides. Results: A broad range of cyclotides specifically interact with membranes containing phosphatidylethanolamine (PE)-phospholipids. Conclusion: Cyclotide bioactivity correlates with an ability to target, insert into, and disrupt lipid membranes containing PE-phospholipids. Significance: Cyclotides constitute a new lipid-binding protein family that has potential as a scaffold to target tumor cells.

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Temperature and Composition Dependence of the Interaction of δ-Lysin with Ternary Mixtures of Sphingomyelin/Cholesterol/POPC

Cited by 98 publications

References 75 publications

Partition profile of the nicotinic acetylcholine receptor in lipid domains upon reconstitution

Partition profile of the nicotinic acetylcholine receptor in lipid domains upon reconstitution

Cholesterol is a determinant of the structures of discoidal high density lipoproteins formed by the solubilization of phospholipid membranes by apolipoprotein A-I

Phosphatidylethanolamine Binding Is a Conserved Feature of Cyclotide-Membrane Interactions

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