Modulation of CTP:phosphocholine cytidylyltransferase by membrane curvature elastic stress

Attard, George S.; Templer, Richard H.; Smith, Wendy S.; Hunt, Alan N.; Jackowski, Suzanne

doi:10.1073/pnas.160260697

Cited by 244 publications

(232 citation statements)

References 42 publications

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“…17 Both these parameters are believed to specifically control protein function, membrane stability, phase behavior, and fusion. 111,112 Our model proved able to correctly predict a monolayer curvature typical of type-0, bilayer-forming lipids for DMPC. Through the second integral moment of the pressure profile, we computed the Gaussian curvature modulus, which, in general, describes the energy required to change the Gaussian curvature of a surface.…”

Section: Discussionmentioning

confidence: 85%

A Quantitative Coarse-Grain Model for Lipid Bilayers

et al. 2007

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A simplified particle-based computer model for hydrated phospholipid bilayers has been developed and applied to quantitatively predict the major physical features of fluid-phase biomembranes. Compared with available coarse-grain methods, three novel aspects are introduced. First, the main electrostatic features of the system are incorporated explicitly via charges and dipoles. Second, water is accurately (yet efficiently) described, on an individual level, by the soft sticky dipole model. Third, hydrocarbon tails are modeled using the anisotropic Gay-Berne potential. Simulations are conducted by rigid-body molecular dynamics. Our technique proves 2 orders of magnitude less demanding of computational resources than traditional atomic-level methodology. Self-assembled bilayers quantitatively reproduce experimental observables such as electron density, compressibility moduli, dipole potential, lipid diffusion, and water permeability. The lateral pressure profile has been calculated, along with the elastic curvature constants of the Helfrich expression for the membrane bending energy; results are consistent with experimental estimates and atomic-level simulation data. Several of the results presented have been obtained for the first time using a coarse-grain method. Our model is also directly compatible with atomic-level force fields, allowing mixed systems to be simulated in a multiscale fashion.

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Section: Discussionmentioning

confidence: 85%

A Quantitative Coarse-Grain Model for Lipid Bilayers

et al. 2007

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“…This has been shown to play a critical role in the energetics of many of the lipid-protein interactions that occur in biological membranes 1,2 . For example, curvature elastic stress, which arises from a system being forced to adopt a curvature that is different from c 0 , has been shown to modulate the activity of many membrane interacting proteins 3,4 and drives the folding of other membrane bound proteins 5,6 . These observations underpin the intrinsic curvature hypothesis, which postulates that cells regulate the composition of their biological membranes so that the net curvature elastic stress is under homeostatic control [7][8][9][10] .…”

Section: Introductionmentioning

confidence: 99%

Lipid Spontaneous Curvatures Estimated from Temperature-Dependent Changes in Inverse Hexagonal Phase Lattice Parameters: Effects of Metal Cations

et al. 2016

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Recently we reported a method for estimating the spontaneous curvatures of lipids from temperature dependent changes in the lattice parameter of inverse hexagonal liquid crystal phases of binary lipid mixtures. This method makes use of 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine, (DOPE) as a host lipid, which preferentially forms an inverse hexagonal phase, to which a guest lipid of unknown spontaneous curvature is added. The lattice parameters of these binary lipid mixtures are determined by small angle X-ray diffraction at a range of temperatures and the spontaneous curvature of the guest lipid is determined from these data. Here we report the use of this method on a wide range of lipids under different ionic conditions. We demonstrate that our method provides spontaneous curvature values for DOPE, cholesterol and monoolein that are within the range of values reported in the literature. Anionic lipids 1,2-dioleoyl-sn-glycerol-3-phosphatidic acid (DOPA) and 1,2-dioleoyl-sn-glycerol-3-phosphoserine (DOPS) were found to exhibit spontaneous curvatures that depend on the concentration of divalent cations present in the mixtures. We show that the range of curvatures estimated experimentally for DOPA and DOPS can be explained by a series of equilibria arising from lipid-cation exchange reactions. Our data indicate a universal relationship between the spontaneous curvature of a lipid and the extent to which it affects the lattice parameter of the hexagonal phase of DOPE when it is part of a binary mixture. This universal relationship affords a rapid way of estimating the spontaneous curvatures of lipids that are expensive, only available in small amounts or are of limited chemical stability.

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“…Next, we addressed the role of curvature in the modulation of lipid-packing defects. Curving a membrane is believed to generate a lateral stress that alters the compact arrangement of the lipids in the bilayer, ultimately leading to the formation of lipid-packing defects that are sensed by peripheral proteins [32][33][34][35][36][37] . This sensing behaviour is illustrated in Fig.…”

Section: Resultsmentioning

confidence: 99%

A sub-nanometre view of how membrane curvature and composition modulate lipid packing and protein recruitment

et al. 2014

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Two parameters of biological membranes, curvature and lipid composition, direct the recruitment of many peripheral proteins to cellular organelles. Although these traits are often studied independently, it is their combination that generates the unique interfacial properties of cellular membranes. Here, we use a combination of in vivo, in vitro and in silico approaches to provide a comprehensive map of how these parameters modulate membrane adhesive properties. The correlation between the membrane partitioning of model amphipathic helices and the distribution of lipid-packing defects in membranes of different shape and composition explains how macroscopic membrane properties modulate protein recruitment by changing the molecular topography of the membrane interfacial region. Furthermore, our results suggest that the range of conditions that can be obtained in a cellular context is remarkably large because lipid composition and curvature have, under most circumstances, cumulative effects.

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Modulation of CTP:phosphocholine cytidylyltransferase by membrane curvature elastic stress

Cited by 244 publications

References 42 publications

A Quantitative Coarse-Grain Model for Lipid Bilayers

A Quantitative Coarse-Grain Model for Lipid Bilayers

Lipid Spontaneous Curvatures Estimated from Temperature-Dependent Changes in Inverse Hexagonal Phase Lattice Parameters: Effects of Metal Cations

A sub-nanometre view of how membrane curvature and composition modulate lipid packing and protein recruitment

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