Modeling lipid raft domains containing a mono-unsaturated phosphatidylethanolamine species

RSC Advances ◽  
2015 ◽  
Vol 5 (47) ◽  
pp. 37102-37111 ◽  
Author(s):  
M. Ferraro ◽  
M. Masetti ◽  
M. Recanatini ◽  
A. Cavalli ◽  
G. Bottegoni
Keyword(s):  
Membrane Protein ◽  
Lipid Rafts ◽  
Protein Interactions ◽  
Lipid Raft ◽  
Coarse Grained ◽  
Coarse Grained Model ◽  
Raft Domains

An advanced coarse-grained model for “atypical” lipid rafts was built and validated to be employed in studies of membrane-protein interactions.

scholarly journals Membrane-Protein Interactions in a Generic Coarse-Grained Model for Lipid Bilayers

2009 ◽  
Vol 96 (1) ◽  
pp. 101-115 ◽  
Author(s):  
Beate West ◽  
Frank L.H. Brown ◽  
Friederike Schmid
Keyword(s):  
Membrane Protein ◽  
Lipid Bilayers ◽  
Protein Interactions ◽  
Coarse Grained ◽  
Coarse Grained Model

scholarly journals Regulation of Latent Membrane Protein 1 Signaling through Interaction with Cytoskeletal Proteins

2015 ◽  
Vol 89 (14) ◽  
pp. 7277-7290 ◽  
Author(s):  
Kirsten Holthusen ◽  
Pooja Talaty ◽  
David N. Everly
Keyword(s):  
Membrane Protein ◽  
Lipid Rafts ◽  
Lipid Raft ◽  
Latent Membrane Protein ◽  
Latent Membrane Protein 1 ◽  
Genome Wide ◽  
A Genome ◽  
Associated Proteins ◽  
Infected Cells ◽  
Raft Domains

ABSTRACTLatent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) induces constitutive signaling in EBV-infected cells to ensure the survival of the latently infected cells. LMP1 is localized to lipid raft domains to induce signaling. In the present study, a genome-wide screen based on bimolecular fluorescence complementation (BiFC) was performed to identify LMP1-binding proteins. Several actin cytoskeleton-associated proteins were identified in the screen. Overexpression of these proteins affected LMP1-induced signaling. BiFC between the identified proteins and LMP1 was localized to lipid raft domains and was dependent on LMP1-induced signaling. Proximity biotinylation assays with LMP1 induced biotinylation of the actin-associated proteins, which were shifted in molecular mass. Together, the findings of this study suggest that the association of LMP1 with lipid rafts is mediated at least in part through interactions with the actin cytoskeleton.IMPORTANCELMP1 signaling requires oligomerization, lipid raft partitioning, and binding to cellular adaptors. The current study utilized a genome-wide screen to identify several actin-associated proteins as candidate LMP1-binding proteins. The interaction between LMP1 and these proteins was localized to lipid rafts and dependent on LMP1 signaling. This suggests that the association of LMP1 with lipid rafts is mediated through interactions with actin-associated proteins.

Nanodomains in biological membranes

2015 ◽  
Vol 57 ◽  
pp. 93-107 ◽  
Author(s):  
Yuanqing Ma ◽  
Elizabeth Hinde ◽  
Katharina Gaus
Keyword(s):  
Lipid Rafts ◽  
T Cell Activation ◽  
Protein Interactions ◽  
Lipid Raft ◽  
Cell Activation ◽  
Imaging Techniques ◽  
Cell Signalling ◽  
Recent Developments ◽  
Lipid Protein Interactions ◽  
High Dynamics

Lipid rafts are defined as cholesterol- and sphingomyelin-enriched membrane domains in the plasma membrane of cells that are highly dynamic and cannot be resolved with conventional light microscopy. Membrane proteins that are embedded in the phospholipid matrix can be grouped into raft and non-raft proteins based on their association with detergent-resistant membranes in biochemical assays. Selective lipid–protein interactions not only produce heterogeneity in the membrane, but also cause the spatial compartmentalization of membrane reactions. It has been proposed that lipid rafts function as platforms during cell signalling transduction processes such as T-cell activation (see Chapter 13 (pages 165–175)). It has been proposed that raft association co-localizes specific signalling proteins that may yield the formation of the observed signalling microclusters at the immunological synapses. However, because of the nanometre size and high dynamics of lipid rafts, direct observations have been technically challenging, leading to an ongoing discussion of the lipid raft model and its alternatives. Recent developments in fluorescence imaging techniques have provided new opportunities to investigate the organization of cell membranes with unprecedented spatial resolution. In this chapter, we describe the concept of the lipid raft and alternative models and how new imaging technologies have advanced these concepts.

scholarly journals Glucosylhydroxyceramides Modulate Secretion Machinery of a Subset of Plasmodesmata Proteins and a Change in the Callose Accumulation

2020 ◽  
Author(s):  
Arya Bagus Boedi Iswanto ◽  
Jong Cheol Shon ◽  
Minh Huy Vu ◽  
Ritesh Kumar ◽  
Kwang Hyeon Liu ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Lipid Rafts ◽  
Lipid Raft ◽  
Protein Trafficking ◽  
Intracellular Trafficking ◽  
Plasma Membranes ◽  
Sphingolipid Metabolism ◽  
Callose Deposition ◽  
Membrane Protein Trafficking ◽  
Underlying Processes

AbstractThe plasma membranes encapsulated in the plasmodesmata (PDs) with symplasmic nano-channels contain abundant lipid rafts, which are enriched by sphingolipids and sterols. The attenuation of sterol compositions has demonstrated the role played by lipid raft integrity in the intercellular trafficking of glycosylphosphatidylinositol (GPI)-anchored PD proteins, particularly affecting in the callose enhancement. The presence of callose at PD is tightly attributed to the callose metabolic enzymes, callose synthases (CalSs) and β-1,3-glucanases (BGs) in regulating callose accumulation and callose degradation, respectively. Sphingolipids have been implicated in signaling and membrane protein trafficking, however the underlying processes linking sphingolipid compositions to the control of symplasmic apertures remain unknown. A wide variety of sphingolipids in plants prompts us to investigate which sphingolipid molecules are important in regulating symplasmic apertures. Here, we demonstrate that perturbations of sphingolipid metabolism by introducing several potential sphingolipid (SL) pathway inhibitors and genetically modifying SL contents from two independent SL pathway mutants are able to modulate callose deposition to control symplasmic connectivity. Our data from pharmacological and genetic approaches show that the alteration in glucosylhydroxyceramides (GlcHCers) particularly disturb the secretory machinery for GPI-anchored PdBG2 protein, resulting in an over accumulated callose. Moreover, our results reveal that SL-enriched lipid rafts link symplasmic channeling to PD callose homeostasis by controlling the targeting of GPI-anchored PdBG2. This study elevates our understanding of the molecular linkage underlying intracellular trafficking and precise targeting to specific destination of GPI-anchored PD proteins incorporated with GlcHCers contents.

Cholesterol sequestration by xenon nano bubbles leads to lipid raft destabilization

Soft Matter ◽  
2020 ◽  
Vol 16 (42) ◽  
pp. 9655-9661
Author(s):  
A. D. Reyes-Figueroa ◽  
Mikko Karttunen ◽  
J. C. Ruiz-Suárez
Keyword(s):  
Molecular Dynamics ◽  
Lipid Rafts ◽  
Lipid Raft ◽  
Md Simulations ◽  
Coarse Grained

Combined coarse-grained (CG) and atomistic molecular dynamics (MD) simulations were performed to study the interactions of xenon with model lipid rafts consisting of DPPC, DLPC and Chol.

scholarly journals Molecular determinants of the interactions between proteins and ssDNA

2015 ◽  
Vol 112 (16) ◽  
pp. 5033-5038 ◽  
Author(s):  
Garima Mishra ◽  
Yaakov Levy
Keyword(s):  
Conformational Changes ◽  
Protein Interactions ◽  
Binding Pocket ◽  
Dna Bases ◽  
Coarse Grained ◽  
Binding Modes ◽  
Ssdna Binding ◽  
Coarse Grained Model ◽  
Molecular Determinants ◽  
Ssdna Binding Proteins

ssDNA binding proteins (SSBs) protect ssDNA from chemical and enzymatic assault that can derail DNA processing machinery. Complexes between SSBs and ssDNA are often highly stable, but predicting their structures is challenging, mostly because of the inherent flexibility of ssDNA and the geometric and energetic complexity of the interfaces that it forms. Here, we report a newly developed coarse-grained model to predict the structure of SSB–ssDNA complexes. The model is successfully applied to predict the binding modes of six SSBs with ssDNA strands of lengths of 6–65 nt. In addition to charge–charge interactions (which are often central to governing protein interactions with nucleic acids by means of electrostatic complementarity), an essential energetic term to predict SSB–ssDNA complexes is the interactions between aromatic residues and DNA bases. For some systems, flexibility is required from not only the ssDNA but also, the SSB to allow it to undergo conformational changes and the penetration of the ssDNA into its binding pocket. The association mechanisms can be quite varied, and in several cases, they involve the ssDNA sliding along the protein surface. The binding mechanism suggests that coarse-grained models are appropriate to study the motion of SSBs along ssDNA, which is expected to be central to the function carried out by the SSBs.

scholarly journals Kinetic frustration by limited bond availability controls the LAT protein condensation phase transition on membranes

2021 ◽  
Author(s):  
Simou Sun ◽  
Trevor GrandPre ◽  
David T. Limmer ◽  
Jay T. Groves
Keyword(s):  
Phase Transition ◽  
T Cell Activation ◽  
Protein Interactions ◽  
Cell Activation ◽  
Coarse Grained ◽  
Structural Basis ◽  
Protein Protein Interactions ◽  
Kinetic Measurements ◽  
Coarse Grained Model ◽  
Intrinsically Disordered

AbstractLAT is a membrane-linked scaffold protein that undergoes a phase transition to form a two-dimensional protein condensate on the membrane during T cell activation. Governed by tyrosine phosphorylation, LAT recruits various proteins that ultimately enable condensation through a percolation network of discrete and selective protein-protein interactions. Here we describe detailed kinetic measurements of the phase transition, along with coarse-grained model simulations, that reveal LAT condensation is kinetically frustrated by the availability of bonds to form the network. Unlike typical miscibility transitions in which compact domains may coexist at equilibrium, the LAT condensates are dynamically arrested in extended states, kinetically trapped out of equilibrium. Modeling identifies the structural basis for this kinetic arrest as the formation of spindle arrangements, favored by limited multivalent binding interactions along the flexible, intrinsically disordered LAT protein. These results reveal how local factors controlling the kinetics of LAT condensation enable formation of different, stable condensates, which may ultimately coexist within the cell.

scholarly journals Quantitative analysis of membrane-mediated interactions and aggregation of flexible peripheral proteins orchestrating large-scale membrane remodeling

2021 ◽  
Author(s):  
Mohsen Sadeghi ◽  
Frank Noe
Keyword(s):  
Protein Interactions ◽  
Large Scale ◽  
Effective Interaction ◽  
Bilayer Membrane ◽  
Coarse Grained ◽  
Membrane Remodeling ◽  
Coarse Grained Model ◽  
Sequence Of Events ◽  
Peripheral Proteins ◽  
The Stability

Shaping and remodeling of biomembranes is essential for cellular trafficking, with membrane-binding peripheral proteins playing the key role in it. Significant membrane remodeling as in endo- and exocytosis is often due to clusters or aggregates of many proteins whose interactions may be direct or mediated via the membrane. While computer simulation could be an important tool to disentangle these interactions and understand what drives cooperative protein interactions in membrane remodeling, this has so far been extremely challenging: protein-membrane systems involve time- and lengthscales that make detailed atomistic simulations impractical, while most coarse-grained models lack the degree of detail needed to resolve the dynamics and physical effect of protein and membrane flexibility. Here, we develop a coarse-grained model of the bilayer membrane bestrewed with rotationally-symmetric flexible membrane-bound proteins. We show how this model can be parameterized based on local curvatures, protein flexibility, and the in-plane dynamics of proteins. We measure the effective interaction potential for the membrane-mediated interactions between peripheral proteins. Furthermore, we investigate the kinetics, equilibrium distributions, and the free energy landscape governing the formation and break-up of protein clusters on the surface of the membrane. We demonstrate how the flexibility of the protein plays a deciding role in highly selective macroscopic aggregation behavior. Finally, we present large-scale simulations of membrane tubulation, and discuss the sequence of events and the stability of intermediates.

scholarly journals Liquid network connectivity regulates the stability and composition of biomolecular condensates with many components

2020 ◽  
Vol 117 (24) ◽  
pp. 13238-13247 ◽  
Author(s):  
Jorge R. Espinosa ◽  
Jerelle A. Joseph ◽  
Ignacio Sanchez-Burgos ◽  
Adiran Garaizar ◽  
Daan Frenkel ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Critical Points ◽  
Network Connectivity ◽  
Coarse Grained ◽  
Physical Parameters ◽  
Protein Protein Interactions ◽  
Coarse Grained Model ◽  
Bond Network ◽  
The Stability ◽  
Liquid Liquid Phase Separation

One of the key mechanisms used by cells to control the spatiotemporal organization of their many components is the formation and dissolution of biomolecular condensates through liquid–liquid phase separation (LLPS). Using a minimal coarse-grained model that allows us to simulate thousands of interacting multivalent proteins, we investigate the physical parameters dictating the stability and composition of multicomponent biomolecular condensates. We demonstrate that the molecular connectivity of the condensed-liquid network—i.e., the number of weak attractive protein–protein interactions per unit of volume—determines the stability (e.g., in temperature, pH, salt concentration) of multicomponent condensates, where stability is positively correlated with connectivity. While the connectivity of scaffolds (biomolecules essential for LLPS) dominates the phase landscape, introduction of clients (species recruited via scaffold–client interactions) fine-tunes it by transforming the scaffold–scaffold bond network. Whereas low-valency clients that compete for scaffold–scaffold binding sites decrease connectivity and stability, those that bind to alternate scaffold sites not required for LLPS or that have higher-than-scaffold valencies form additional scaffold–client–scaffold bridges increasing stability. Proteins that establish more connections (via increased valencies, promiscuous binding, and topologies that enable multivalent interactions) support the stability of and are enriched within multicomponent condensates. Importantly, proteins that increase the connectivity of multicomponent condensates have higher critical points as pure systems or, if pure LLPS is unfeasible, as binary scaffold–client mixtures. Hence, critical points of accessible systems (i.e., with just a few components) might serve as a unified thermodynamic parameter to predict the composition of multicomponent condensates.

scholarly journals Compartmentalization of the Exocyst Complex in Lipid Rafts Controls Glut4 Vesicle Tethering

2006 ◽  
Vol 17 (5) ◽  
pp. 2303-2311 ◽  
Author(s):  
Mayumi Inoue ◽  
Shian-Huey Chiang ◽  
Louise Chang ◽  
Xiao-Wei Chen ◽  
Alan R. Saltiel
Keyword(s):  
Plasma Membrane ◽  
Glucose Uptake ◽  
Lipid Rafts ◽  
Lipid Raft ◽  
Pdz Domain ◽  
Vesicle Tethering ◽  
Exocyst Complex ◽  
Raft Domains ◽  
Lipid Raft Microdomains ◽  
Stimulation Of

Lipid raft microdomains act as organizing centers for signal transduction. We report here that the exocyst complex, consisting of Exo70, Sec6, and Sec8, regulates the compartmentalization of Glut4-containing vesicles at lipid raft domains in adipocytes. Exo70 is recruited by the G protein TC10 after activation by insulin and brings with it Sec6 and Sec8. Knockdowns of these proteins block insulin-stimulated glucose uptake. Moreover, their targeting to lipid rafts is required for glucose uptake and Glut4 docking at the plasma membrane. The assembly of this complex also requires the PDZ domain protein SAP97, a member of the MAGUKs family, which binds to Sec8 upon its translocation to the lipid raft. Exocyst assembly at lipid rafts sets up targeting sites for Glut4 vesicles, which transiently associate with these microdomains upon stimulation of cells with insulin. These results suggest that the TC10/exocyst complex/SAP97 axis plays an important role in the tethering of Glut4 vesicles to the plasma membrane in adipocytes.

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