scholarly journals Lipid-mediated Association of the Slg1 Transmembrane Domains in Yeast Plasma Membranes

2021 ◽  
Author(s):  
Azadeh Alavizargar ◽  
Annegret Eltig ◽  
Roland Wedlich Soeldner ◽  
Andreas Heuer
Keyword(s):  
Plasma Membrane ◽  
Protein Interactions ◽  
Plasma Membranes ◽  
Acyl Chain ◽  
Md Simulations ◽  
Receptor Activation ◽  
Transmembrane Domains ◽  
Coarse Grained ◽  
Self Association ◽  
Lipid Protein Interactions

Clustering of transmembrane proteins underlies a multitude of fundamental biological processes at the plasma membrane such as receptor activation, lateral domain formation and mechanotransduction. The self-association of the respective transmembrane domains (TMD) has also been suggested to be responsible for the micron-scaled patterns seen for integral membrane proteins in the budding yeast plasma membrane (PM). However, the underlying interplay between local lipid composition and TMD identity is still not mechanistically understood. In this work we have used coarse-grained molecular dynamics (MD) simulations as well as microscopy experiments (TIRFM) to analyze the behavior of a representative helical yeast TMD (Slg1) within different lipid environments. Via the simulations we evaluated the effect of acyl chain saturation and the presence of anionic lipids head groups on the association of TMDs via simulations. Our simulations revealed that weak lipid-protein interactions significantly affect the configuration of TMD dimers and the free energy of association. Increased amounts of unsaturated phospholipids strongly reduced helix-helix interaction and the presence of phosphatidylserine (PS) lipids only slightly affected the dimer. Experimentally, the network factor, characterizing the association strength on a mesoscopic level, was measured in the presence and absence of PS lipids. Consistently with the simulations, no significant effect was observed. We also found that formation of TMD dimers in turn increased the order parameter of the surrounding lipids and induced long-range perturbations in lipid organization, shedding new light on the lipid-mediated dimerization of TMDs in complex lipid mixtures.

scholarly journals Computational Study of C-X-C Chemokine Receptor (CXCR)3 Binding with Its Natural Agonists Chemokine (C-X-C Motif) Ligand (CXCL)9, 10 and 11 and with Synthetic Antagonists: Insights of Receptor Activation towards Drug Design for Vitiligo

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4413
Author(s):  
Giovanny Aguilera-Durán ◽  
Antonio Romo-Mancillas
Keyword(s):  
Molecular Dynamics ◽  
Computational Study ◽  
Md Simulations ◽  
Receptor Activation ◽  
Activation Mechanism ◽  
Coarse Grained ◽  
Dimensional Structure ◽  
Cytotoxic Lymphocytes ◽  
Ligand Interaction ◽  
Α Subunit

Vitiligo is a hypopigmentary skin pathology resulting from the death of melanocytes due to the activity of CD8+ cytotoxic lymphocytes and overexpression of chemokines. These include CXCL9, CXCL10, and CXCL11 and its receptor CXCR3, both in peripheral cells of the immune system and in the skin of patients diagnosed with vitiligo. The three-dimensional structure of CXCR3 and CXCL9 has not been reported experimentally; thus, homology modeling and molecular dynamics could be useful for the study of this chemotaxis-promoter axis. In this work, a homology model of CXCR3 and CXCL9 and the structure of the CXCR3/Gαi/0βγ complex with post-translational modifications of CXCR3 are reported for the study of the interaction of chemokines with CXCR3 through all-atom (AA-MD) and coarse-grained molecular dynamics (CG-MD) simulations. AA-MD and CG-MD simulations showed the first activation step of the CXCR3 receptor with all chemokines and the second activation step in the CXCR3-CXCL10 complex through a decrease in the distance between the chemokine and the transmembrane region of CXCR3 and the separation of the βγ complex from the α subunit in the G-protein. Additionally, a general protein–ligand interaction model was calculated, based on known antagonists binding to CXCR3. These results contribute to understanding the activation mechanism of CXCR3 and the design of new molecules that inhibit chemokine binding or antagonize the receptor, provoking a decrease of chemotaxis caused by the CXCR3/chemokines axis.

scholarly journals Spontaneous Membrane Nanodomain Formation in the Absence or Presence of the Neurotransmitter Serotonin

2020 ◽  
Vol 8 ◽  
Author(s):  
Anna Bochicchio ◽  
Astrid F. Brandner ◽  
Oskar Engberg ◽  
Daniel Huster ◽  
Rainer A. Böckmann
Keyword(s):  
Phase Transition ◽  
Plasma Membrane ◽  
Specific Binding ◽  
Signal Transmission ◽  
Acyl Chain ◽  
Md Simulations ◽  
High Temporal Resolution ◽  
Detailed Knowledge ◽  
Transient Nature ◽  
Different Temperatures

Detailed knowledge on the formation of biomembrane domains, their structure, composition, and physical characteristics is scarce. Despite its frequently discussed importance in signaling, e.g., in obtaining localized non-homogeneous receptor compositions in the plasma membrane, the nanometer size as well as the dynamic and transient nature of domains impede their experimental characterization. In turn, atomistic molecular dynamics (MD) simulations combine both, high spatial and high temporal resolution. Here, using microsecond atomistic MD simulations, we characterize the spontaneous and unbiased formation of nano-domains in a plasma membrane model containing phosphatidylcholine (POPC), palmitoyl-sphingomyelin (PSM), and cholesterol (Chol) in the presence or absence of the neurotransmitter serotonin at different temperatures. In the ternary mixture, highly ordered and highly disordered domains of similar composition coexist at 303 K. The distinction of domains by lipid acyl chain order gets lost at lower temperatures of 298 and 294 K, suggesting a phase transition at ambient temperature. By comparison of domain ordering and composition, we demonstrate how the domain-specific binding of the neurotransmitter serotonin results in a modified domain lipid composition and a substantial downward shift of the phase transition temperature. Our simulations thus suggest a novel mode of action of neurotransmitters possibly of importance in neuronal signal transmission.

scholarly journals Lipid Headgroup Charge and Acyl Chain Composition Modulate Closure of Bacterial β-Barrel Channels

2019 ◽  
Vol 20 (3) ◽  
pp. 674 ◽  
Author(s):  
D. Perini ◽  
Antonio Alcaraz ◽  
María Queralt-Martín
Keyword(s):  
Membrane Permeability ◽  
Outer Membrane ◽  
Protein Interactions ◽  
Membrane Lipids ◽  
Acyl Chain ◽  
Extensive Study ◽  
Electrophysiological Recordings ◽  
Sequential Closure ◽  
Lipid Protein Interactions ◽  
Outer Membrane Permeability

The outer membrane of Gram-negative bacteria contains β-barrel proteins that form high-conducting ion channels providing a path for hydrophilic molecules, including antibiotics. Traditionally, these proteins have been considered to exist only in an open state so that regulation of outer membrane permeability was accomplished via protein expression. However, electrophysiological recordings show that β-barrel channels respond to transmembrane voltages by characteristically switching from a high-conducting, open state, to a so-called ‘closed’ state, with reduced permeability and possibly exclusion of large metabolites. Here, we use the bacterial porin OmpF from E. coli as a model system to gain insight on the control of outer membrane permeability by bacterial porins through the modulation of their open state. Using planar bilayer electrophysiology, we perform an extensive study of the role of membrane lipids in the OmpF channel closure by voltage. We pay attention not only to the effects of charges in the hydrophilic lipid heads but also to the contribution of the hydrophobic tails in the lipid-protein interactions. Our results show that gating kinetics is governed by lipid characteristics so that each stage of a sequential closure is different from the previous one, probably because of intra- or intermonomeric rearrangements.

scholarly journals Haemolytic actinoporins interact with carbohydrates using their lipid-binding module

2017 ◽  
Vol 372 (1726) ◽  
pp. 20160216 ◽  
Author(s):  
Koji Tanaka ◽  
Jose M. M. Caaveiro ◽  
Koldo Morante ◽  
Kouhei Tsumoto
Keyword(s):  
Protein Interactions ◽  
Pore Formation ◽  
Plasma Membranes ◽  
Lipid Binding ◽  
Target Cells ◽  
Sea Anemones ◽  
Molecular Systems ◽  
Membrane Pores ◽  
Living Organisms ◽  
Lipid Protein Interactions

Pore-forming toxins (PFTs) are proteins endowed with metamorphic properties that enable them to stably fold in water solutions as well as in cellular membranes. PFTs produce lytic pores on the plasma membranes of target cells conducive to lesions, playing key roles in the defensive and offensive molecular systems of living organisms. Actinoporins are a family of potent haemolytic toxins produced by sea anemones vigorously studied as a paradigm of α-helical PFTs, in the context of lipid–protein interactions, and in connection with nanopore technologies. We have recently reported that fragaceatoxin C (FraC), an actinoporin, engages biological membranes with a large adhesive motif allowing the simultaneous attachment of up to four lipid molecules prior to pore formation. Since actinoporins also interact with carbohydrates, we sought to understand the molecular and energetic basis of glycan recognition by FraC. By employing structural and biophysical methodologies, we show that FraC engages glycans with low affinity using its lipid-binding module. Contrary to other PFTs requiring separate domains for glycan and lipid recognition, the small single-domain actinoporins economize resources by achieving dual recognition with a single binding module. This mechanism could enhance the recruitment of actinoporins to the surface of target tissues in their marine environment. This article is part of the themed issue ‘Membrane pores: from structure and assembly, to medicine and technology’.

Lipid–Protein Interactions in Plasma Membrane Organization and Function

2022 ◽  
Vol 51 (1) ◽  
Author(s):  
Taras Sych ◽  
Kandice R. Levental ◽  
Erdinc Sezgin
Keyword(s):  
Plasma Membrane ◽  
Protein Interactions ◽  
Collective Behavior ◽  
Protein Function ◽  
Lipid Binding ◽  
Publication Date ◽  
Membrane Organization ◽  
Lipid Protein Interactions ◽  
And Function ◽  
Specific Lipid

Lipid–protein interactions in cells are involved in various biological processes, including metabolism, trafficking, signaling, host–pathogen interactions, and transmembrane transport. At the plasma membrane, lipid–protein interactions play major roles in membrane organization and function. Several membrane proteins have motifs for specific lipid binding, which modulate protein conformation and consequent function. In addition to such specific lipid–protein interactions, protein function can be regulated by the dynamic, collective behavior of lipids in membranes. Emerging analytical, biochemical, and computational technologies allow us to study the influence of specific lipid–protein interactions, as well as the collective behavior of membranes on protein function. In this article, we review the recent literature on lipid–protein interactions with a specific focus on the current state-of-the-art technologies that enable novel insights into these interactions. Expected final online publication date for the Annual Review of Biophysics, Volume 51 is May 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The Origin of the Eukaryotic Cell Based on Conservation of Existing Interfaces

2006 ◽  
Vol 12 (4) ◽  
pp. 513-523 ◽  
Author(s):  
Albert D. G. de Roos
Keyword(s):  
Plasma Membrane ◽  
Protein Interactions ◽  
Self Assembly ◽  
Evolutionary Model ◽  
Lipid Vesicles ◽  
Eukaryotic Cell ◽  
The Self ◽  
Lipid Protein Interactions

Current theories about the origin of the eukaryotic cell all assume that during evolution a prokaryotic cell acquired a nucleus. Here, it is shown that a scenario in which the nucleus acquired a plasma membrane is inherently less complex because existing interfaces remain intact during evolution. Using this scenario, the evolution to the first eukaryotic cell can be modeled in three steps, based on the self-assembly of cellular membranes by lipid-protein interactions. First, the inclusion of chromosomes in a nuclear membrane is mediated by interactions between laminar proteins and lipid vesicles. Second, the formation of a primitive endoplasmic reticulum, or exomembrane, is induced by the expression of intrinsic membrane proteins. Third, a plasma membrane is formed by fusion of exomembrane vesicles on the cytoskeletal protein scaffold. All three self-assembly processes occur both in vivo and in vitro. This new model provides a gradual Darwinistic evolutionary model of the origins of the eukaryotic cell and suggests an inherent ability of an ancestral, primitive genome to induce its own inclusion in a membrane.

A review of traditional and emerging methods to characterize lipid–protein interactions in biological membranes

2015 ◽  
Vol 7 (17) ◽  
pp. 7076-7094 ◽  
Author(s):  
Chih-Yun Hsia ◽  
Mark J. Richards ◽  
Susan Daniel
Keyword(s):  
Plasma Membrane ◽  
Membrane Protein ◽  
Protein Interactions ◽  
Protein Structures ◽  
Biological Membranes ◽  
Biological Functions ◽  
Cell Plasma Membrane ◽  
Lipid Interactions ◽  
Cell Plasma ◽  
Lipid Protein Interactions

Lipid–protein interactions are essential for modulating membrane protein structures and biological functions in the cell plasma membrane. In this review we describe the salient features of classical and emerging methodologies for studying protein–lipid interactions and their limitations.

scholarly journals Lipid-Protein Interactions in Fiber Cell Plasma Membrane Isolated From Human and Porcine Eye Lenses

2017 ◽  
Vol 112 (3) ◽  
pp. 319a
Author(s):  
Marija Raguz ◽  
Laxman Mainali ◽  
William J. O‘Brien ◽  
Witold Karol Subczynski
Keyword(s):  
Plasma Membrane ◽  
Protein Interactions ◽  
Fiber Cell ◽  
Cell Plasma Membrane ◽  
Cell Plasma ◽  
Lipid Protein Interactions

Spin-label studies of lipid-protein interactions with reconstituted band 3, the human erythrocyte chloride-bicarbonate exchanger

1998 ◽  
Vol 76 (5) ◽  
pp. 815-822 ◽  
Author(s):  
Andrew M Taylor ◽  
Anthony Watts
Keyword(s):  
Electron Paramagnetic Resonance ◽  
Protein Interactions ◽  
Spin Label ◽  
Acyl Chain ◽  
Lateral Diffusion ◽  
Band 3 ◽  
Paramagnetic Resonance ◽  
A Value ◽  
Lipid Protein Interactions ◽  
Electron Paramagnetic

Lipid-protein interactions in reconstituted band 3 preparations were investigated by using spin-labeled lipids in conjunction with electron paramagnetic resonance (EPR) spectroscopy. Purified erythrocyte band 3 was reconstituted into egg phosphatidylcholine liposomes at high protein density with preservation predominantly of the dimeric state. Lipid-protein associations were revealed by the presence of a component in the EPR spectra that, when compared to spectra obtained from protein-free bilayers, indicated that lipid chain motions are restricted by interactions with the protein. From the fraction of the motionally restricted component obtained from the phosphatidylcholine spin-label, a value of 64 ± 14 annular lipids per band 3 dimer was obtained. This agrees with a value of 62 for the number of lipids that may be accommodated around the electron density map of a band 3 dimer. Selectivity of various spin-labeled lipids for the protein revealed that androstanol had a lower affinity for the band 3 interface, whereas a distinct preference was observed for the negatively charged lipids phosphatidylglycerol and stearic acid over phosphatidylcholine. This preference for negatively charged lipids could not be screened by 1-M salt, indicating that electrostatic lipid-protein interactions are not dominant. Estimates of annular lipid exchange rates from measured acyl chain segmental motions suggested that the rate of exchange between bilayer and boundary lipids was ~106 s-1, at least an order of magnitude slower than the rate of lipid lateral diffusion in protein-free bilayers.Key words: band 3, reconstitution, electron paramagnetic resonance, lipid-protein interactions.

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