Lipid–Protein Interactions Are Unique Fingerprints for Membrane Proteins

Corradi, Valentina; Mendez-Villuendas, Eduardo; Ingólfsson, Helgi I.; Gu, Ruo‐Xu; Siuda, Iwona; Melo, Manuel N.; Moussatova, Anastassiia; DeGagné, Lucien J.; Sejdiu, Besian I.; Singh, G.; Wassenaar, Tsjerk A.; Magnero, Karelia Delgado; Marrink, Siewert J.; Tieleman, D. Peter

doi:10.1021/acscentsci.8b00143

Cited by 288 publications

(271 citation statements)

References 110 publications

(195 reference statements)

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“…phosphatidylinositol (4,5) bis-phosphate (PIP 2 ) bound to Kir channels [27,28]; cardiolipin (CDL) bound to the ADP/ATP carrier [29,30], and to the LeuT transporter [1]; and PIP 2 bound to Class A GPCRS [31] and to TRP channels [32]. MD simulations can also provide information on local enrichment of various lipid species in the bilayer around a given membrane protein [33].…”

Section: Protein-lipid Interactions: Structures and Simulationsmentioning

confidence: 99%

The energetics of protein–lipid interactions as viewed by molecular simulations

Corey

Stansfeld

Sansom

2019

Biochemical Society Transactions

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Membranes are formed from a bilayer containing diverse lipid species with which membrane proteins interact. Integral, membrane proteins are embedded in this bilayer, where they interact with lipids from their surroundings, whilst peripheral membrane proteins bind to lipids at the surface of membranes. Lipid interactions can influence the function of membrane proteins, either directly or allosterically. Both experimental (structural) and computational approaches can reveal lipid binding sites on membrane proteins. It is, therefore, important to understand the free energies of these interactions. This affords a more complete view of the engagement of a particular protein with the biological membrane surrounding it. Here, we describe many computational approaches currently in use for this purpose, including recent advances using both free energy and unbiased simulation methods. In particular, we focus on interactions of integral membrane proteins with cholesterol, and with anionic lipids such as phosphatidylinositol 4,5-bis-phosphate and cardiolipin. Peripheral membrane proteins are exemplified via interactions of PH domains with phosphoinositide-containing membranes. We summarise the current state of the field and provide an outlook on likely future directions of investigation.

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Section: Protein-lipid Interactions: Structures and Simulationsmentioning

confidence: 99%

The energetics of protein–lipid interactions as viewed by molecular simulations

Corey

Stansfeld

Sansom

2019

Biochemical Society Transactions

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“…LTPs transport lipids from one membrane to another, and we hypothesize that regulatory transport mainly takes place with the endoplasmic reticulum (ER). For simplicity, we also discard effects of other proteins present in biological membranes (24). Figure 1: (A) Sketch of the regulatory processes used for our argument.…”

Section: Regulated Ensembles As a Collection Of Semi-grand Canonical mentioning

confidence: 99%

Regulating lipid composition rationalizes acyl-tail saturation homeostasis in ectotherms

Girard

Bereau

2019

Preprint

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Cell membranes mainly consist of lipid bilayers with an actively regulated composition. The underlying processes are still poorly understood, in particular how the hundreds of components are controlled. Surprisingly, in recent experiments on ectotherms, the cholesterol fraction, along with un-and mono-saturated acyl tail fractions and demixing temperatures, was shown to increase with body temperature. We establish a model based on chemical reaction networks to study regulation of membranes, resulting in multiple semi-grand canonical ensembles. By running computer simulations, we show that higher cholesterol fractions correlate with lower degrees of unsaturation, ultimately controlling the composition of lipid tails. Cholesterol also dictates membrane viscosity and regulation of the latter implies that cholesterol must increase with temperature. Overall, our model proposes a different picture of lipid regulation, where components can be passively, instead of actively, regulated. SIGNIFICANCE In this article, we propose a regulation model where only some of the components are actively regulated between membranes, while others are naturally balanced by chemical potentials. This model provides a rationale to recently measured puzzling trends in ectotherms, that is, increased plasma membrane cholesterol fraction with temperature. Here, we show that it is directly correlated with with acyl tail saturation and order parameter correlation length. Furthermore, we highlight the relation between cholesterol and membrane viscosity.

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“…Although the field's focus has been mostly on membrane curvature, lipid packing defects are a more general phenomenon. Due to the heterogeneity of biological membranes, there are many irregularities that may cause disturbances of the local lipid packing in a similar fashion to curvature; e.g., the edges of lipid nanodomains ("rafts") (Schäfer and Marrink, 2010;Nickels et al, 2015;Belička et al, 2017;Park and Im, 2018), membrane junctions [e.g., membrane fusion intermediates (Risselada et al, 2014;Tsai et al, 2014;Smirnova et al, 2019), and transmembrane proteins (Lee, 2003;Corradi et al, 2018)]. In these three examples, the difference in chemical potential imposed by the membrane inhomogeneity alters its surrounding membrane environment, and this has interesting consequences for biological functionality.…”

Section: Introductionmentioning

confidence: 99%