Evidence for phospholipid microdomain formation in liquid crystalline liposomes reconstituted with Escherichia coli lactose permease

Lehtonen, Jukka; Kinnunen, Paavo K.J.

doi:10.1016/s0006-3495(97)78771-x

Cited by 61 publications

(36 citation statements)

References 96 publications

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“…This conclusion is further substantiated by the results of the mixtures of the unsaturated PC species. Also in these systems no molecular sorting takes place under Literature data so far have shown molecular sorting of lipids to occur to various extents for a number of membrane proteins (5)(6)(7)(8). Then why do we not observe it in our systems?…”

Section: Discussionmentioning

confidence: 69%

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Photo-Crosslinking Analysis of Preferential Interactions between a Transmembrane Peptide and Matching Lipids

et al. 2004

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In this study, a novel method is presented by which the molecular environment of a transmembrane peptide can be investigated directly. This was achieved by incorporating a photoactivatable crosslinking probe in the hydrophobic segment of a model transmembrane peptide. When this peptide was incorporated into lipid bilayers and irradiated with UV light, a covalent bond was formed between the crosslinking probe and a lipid. This crosslinking reaction could be visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the resulting product could be characterized by mass spectrometry. By use of phospholipases, it was demonstrated that the peptide crosslinks to both acyl chains of the lipids. The peptide showed a clear preference to partition into fluid lipids and was excluded from lipids in the gel phase. However, when the peptide was incorporated into bilayers containing two lipid species with different acyl chain lengths, molecular sorting of the lipids around the peptide based on hydrophobic matching was not observed. It is proposed that the size of the transmembrane part plays an important role in the dynamic interactions of membrane proteins with the surrounding lipids and hence in determining whether molecular sorting can occur.Proteins in biological membranes reside in a complex environment in which they are surrounded by many different lipid species. Transmembrane proteins can have different affinities for different lipids, and as a result particular lipids or members of particular lipid classes may become enriched around a certain protein. Such differences in affinity may be due to specific interactions with the lipid headgroups or the lipid acyl chains. An example of the latter would be the enrichment of matching lipids around a protein, which could be a mechanism by which mismatches between hydrophobic transmembrane segments and the hydrophobic thickness of the lipid bilayer can be relieved. Such a mechanism of molecular sorting by transmembrane proteins has been predicted from theoretical calculations (1, 2; reviewed in refs 3 and 4) and has indeed been shown to occur for several transmembrane proteins (5-8).To gain insight into the role of protein-lipid interactions in the sorting of lipids around specific proteins, tools must be available to determine the lipid environment of membrane proteins. Previously, this has been probed mainly by fluorescence and ESR 1 methods using labeled lipids (5-11). In this study, we explore a more direct method to investigate the immediate surroundings of membrane proteins. For this purpose we make use of a synthetic model peptide, which contains a photoactivatable probe that is able to form covalent bonds with the surrounding lipids upon UV irradiation. The crosslinking reaction can be visualized by SDS-PAGE analysis and the identity of the lipid that is crosslinked to the peptide can subsequently be characterized by mass spectrometry.

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Section: Discussionmentioning

confidence: 69%

“…Previously, this has been probed mainly by fluorescence and ESR 1 methods using labeled lipids (5)(6)(7)(8)(9)(10)(11). In this study, we explore a more direct method to investigate the immediate surroundings of membrane proteins.…”

mentioning

confidence: 99%

Photo-Crosslinking Analysis of Preferential Interactions between a Transmembrane Peptide and Matching Lipids

et al. 2004

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“…It was found that the smaller the protein, the more pronounced is the tilt. There are few experimental attempts to estimate the extent of the protein-induced bilayer perturbation; nevertheless, the existing ones confirm a qualitative mismatch dependence of the extent of the perturbation [204,207,[226][227][228][229]. Nielsen et al [123] carried out MD simulations on a coarse-grained model to analyze the lipid bilayer perturbation around a transmembrane hydrophobic nanotube.…”

Section: Hydrophobic Mismatchmentioning

confidence: 99%

Mesoscopic models of biological membranes

Venturoli¹,

et al. 2006

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Phospholipids are the main components of biological membranes and dissolved in water these molecules self-assemble into closed structures, of which bilayers are the most relevant from a biological point of view. Lipid bilayers are often used, both in experimental and by theoretical investigations, as model systems to understand the fundamental properties of biomembranes. The properties of lipid bilayers can be studied at different time and length scales. For some properties it is sufficient to envision a membrane as an elastic sheet, while for others it is important to take into account the details of the individual atoms. In this review, we focus on an intermediate level, where groups of atoms are lumped into pseudo-particles to arrive at a coarse-grained, or mesoscopic, description of a bilayer, which is subsequently studied using molecular simulation.The aim of this review is to compare various strategies to coarse grain a biological membrane. The conclusion of this comparison is that there can be many valid different strategies, but that the results obtained by the various mesoscopic models are surprisingly consistent. A second objective of this review is to illustrate how mesoscopic models can be used to obtain a better understanding of experimental systems. The advantage of coarse-grained models is that these can be simulated very efficiently, so that phenomena involving large systems, or requiring a large number of simulations, can be studied in detail. This is illustrated with the study of the relation between the phase behavior of a membrane and the structure of the phospholipids, and the membrane structural changes due to molecules (such as alcohols, cholesterol and anesthetics) adsorbed to the membrane. We then discuss the effect of transmembrane peptides on the local structure of a membrane and the mechanism of vesicle fusion and fission.

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“…Proteins can be routed through the secretory pathway by increasing their hydrophobic thickness via mutagenesis and passing from one membrane to another more closely matching their new length (Pelham and Munro 93). The difference between the hydrophobic length of protein and membrane, denoted hydrophobic mismatch, affects inter alia, lateral segregation of proteins in membranes (Marsh 1995;Lehtonen and Kinnunen 1997), the lipid melting transition (Piknova et al, 1993), and protein activity (Johannsson et al 1981: Froud et al 1986). Hydrophobic mismatch also affects the way in which the stabilty and the inclination of transmembrane helices change as functions of their hydrophobic length.…”

Section: Introductionmentioning

confidence: 99%

Molecular theory of hydrophobic mismatch between lipids and peptides

Duque

Katsov

et al. 2002

The Journal of Chemical Physics

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Effects of the mismatch between the hydrophobic length, d, of transmembrane alpha helices of integral proteins and the hydrophobic thickness, D h , of the membranes they span are studied theoretically utilizing a microscopic model of lipids. In particular, we examine the dependence of the period of a lamellar phase on the hydrophobic length and volume fraction of a rigid, integral, peptide. We find that the period decreases when a short peptide, such that d < D h , is inserted. More surprising, we find that the period increases when a long peptide, such that d > D h , is inserted. The effect is due to the replacement of extensible lipid tails by rigid peptide. As the peptide length is increased, the lamellar period continues to increase, but at a slower rate, and can eventually decrease. The amount of peptide which fails to incorporate and span the membrane increases with the magnitude of the hydrophobic mismatch |d − D h |. We explicate these behaviors which are all in accord with experiment. Predictions are made for the dependence of the tilt of a single trans-membrane alpha helix on hydrophobic mismatch and helix density.

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Evidence for phospholipid microdomain formation in liquid crystalline liposomes reconstituted with Escherichia coli lactose permease

Cited by 61 publications

References 96 publications

Photo-Crosslinking Analysis of Preferential Interactions between a Transmembrane Peptide and Matching Lipids

Photo-Crosslinking Analysis of Preferential Interactions between a Transmembrane Peptide and Matching Lipids

Mesoscopic models of biological membranes

Molecular theory of hydrophobic mismatch between lipids and peptides

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