Lipid flippases and their biological functions

Pomorski, Thomas; Menon, Anant K.

doi:10.1007/s00018-006-6167-7

Cited by 290 publications

(308 citation statements)

References 180 publications

(181 reference statements)

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“…47 An all-atom simulation predicts that the barrier for DPPC flip flop is 75 kJ/mol, 48 a value that matches well the experimental prediction of the barrier. 49 As we do not observe any flip-flop events in our simulations ͑with total time on a millisecond time scale͒, we do not estimate the rate from our model since obviously the activation barrier is quite high. More coarsely grained simulations do observe lipid flip-flop events, 28 consistent with a dramatic lowering of the activation energy for flip flop and hence very large acceleration of the time scale.…”

Section: A Internal Bilayer Time Scalesmentioning

confidence: 79%

An implicit solvent coarse-grained lipid model with correct stress profile

Sodt

Head‐Gordon

2010

The Journal of Chemical Physics

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We develop a coarse-grained parametrization strategy for lipid membranes that we illustrate for a dipalmitoylphosphatidylcholine bilayer. Our coarse-graining approach eliminates the high cost of explicit solvent but maintains more lipid interaction sites. We use a broad attractive tail-tail potential and extract realistic bonded potentials of mean force from all-atom simulations, resulting in a model with a sharp gel to fluid transition, a correct bending modulus, and overall very reasonable dynamics when compared with experiment. We also determine a quantitative stress profile and correct breakdown of contributions from lipid components when compared with detailed all-atom simulation benchmarks, which has been difficult to achieve for implicit membrane models. Such a coarse-grained lipid model will be necessary for efficiently simulating complex constructs of the membrane, such as protein assembly and lipid raft formation, within these nonaqueous chemical environments.

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Section: A Internal Bilayer Time Scalesmentioning

confidence: 79%

An implicit solvent coarse-grained lipid model with correct stress profile

Sodt

Head‐Gordon

2010

The Journal of Chemical Physics

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“…The non-random distribution of phosphatidylserine across the membrane bilayer is due to the energydependent activity of aminophospholipid translocase, a member of the flippase family of enzymes 48 . During apoptosis or cell injury, a rise in intracellular Ca 2+ levels triggers two concomitant events that disrupt this normal arrangement: the inhibition of aminophospholipid translocase and the stimulation of scramblases, enzymes that facilitate the transbilayer randomization of phosphatidylserine 49,50 .…”

Section: Flippasementioning

confidence: 99%

A neuroscientist's guide to lipidomics

2007

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| Nerve cells mould the lipid fabric of their membranes to ease vesicle fusion, regulate ion fluxes and create specialized microenvironments that contribute to cellular communication. The chemical diversity of membrane lipids controls protein traffic, facilitates recognition between cells and leads to the production of hundreds of molecules that carry information both within and across cells. With so many roles, it is no wonder that lipids make up half of the human brain in dry weight. The objective of neural lipidomics is to understand how these molecules work together; this difficult task will greatly benefit from technical advances that might enable the testing of emerging hypotheses.

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“…6,7 To complement active translocation, cells also use passive transport mechanisms that facilitate the migration of lipids from one leaflet to another. For this purpose, the translocation may take place with the help of proteins or without them.…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanism for Lipid Flip-Flops

2007

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Transmembrane lipid translocation (flip-flop) processes are involved in a variety of properties and functions of cell membranes, such as membrane asymmetry and programmed cell death. Yet, flip-flops are one of the least understood dynamical processes in membranes. In this work, we elucidate the molecular mechanism of pore-mediated transmembrane lipid translocation (flip-flop) acquired from extensive atomistic molecular dynamics simulations. On the basis of 50 successful flip-flop events resolved in atomic detail, we demonstrate that lipid flip-flops may spontaneously occur in protein-free phospholipid membranes under physiological conditions through transient water pores on a time scale of tens of nanoseconds. While the formation of a water pore is induced here by a transmembrane ion density gradient, the particular way by which the pore is formed is irrelevant for the reported flip-flop mechanism: the appearance of a transient pore (defect) in the membrane inevitably leads to diffusiVe translocation of lipids through the pore, which is driven by thermal fluctuations. Our findings strongly support the idea that the formation of membrane defects in terms of water pores is the rate-limiting step in the process of transmembrane lipid flip-flop, which, on average, requires several hours. The findings are consistent with available experimental and computational data and provide a view to interpret experimental observations. For example, the simulation results provide a molecular-level explanation in terms of pores for the experimentally observed fact that the exposure of lipid membranes to electric field pulses considerably reduces the time required for lipid flip-flops.

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Lipid flippases and their biological functions

Cited by 290 publications

References 180 publications

An implicit solvent coarse-grained lipid model with correct stress profile

An implicit solvent coarse-grained lipid model with correct stress profile

A neuroscientist's guide to lipidomics

Molecular Mechanism for Lipid Flip-Flops

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