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Membrane fusion

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https://www.readbyqxmd.com/read/28104377/changes-in-lipid-bilayer-structure-caused-by-the-helix-to-sheet-tansition-of-an-hiv-1-gp41-fusion-peptide-derivative
#1
William T Heller, Durgesh K Rai
HIV-1, like other enveloped viruses, undergoes fusion with the cell membrane to infect it. Viral coat proteins are thought to bind the virus to the membrane and actively fuse the viral and cellular membranes together. The actual molecular mechanism of fusion is challenging to visualize, resulting in the use of model systems. Here, the bilayer curvature modifying properties of a synthetic variant of the HIV-1 gp41 fusion peptide with lipid bilayer vesicles composed of a mixture of dimyristoyl phosphatidylcholine (DMPC) and dimyristoyl phosphatidylserine (DMPS) were studied...
January 16, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28103440/carbon-nanotubes-mediate-fusion-of-lipid-vesicles
#2
Ramachandra Moorthy Bhaskara, Stephanie M Linker, Martin Vögele, Juergen Koefinger, Gerhard Hummer
The fusion of lipid membranes is opposed by high energetic barriers. In living organisms, complex protein machineries carry out this biologically essential process. Here we show that membrane-spanning carbon nanotubes (CNTs) can trigger spontaneous fusion of small lipid vesicles. In coarse-grained molecular dynamics simulations, we find that a CNT bridging between two vesicles locally perturbs their lipid structure. Their outer leaflets merge as the CNT pulls lipids out of the membranes, creating an hourglass-shaped fusion intermediate with still intact inner leaflets...
January 19, 2017: ACS Nano
https://www.readbyqxmd.com/read/28102911/glutathione-peroxidase-like-enzymes-cover-five-distinct-cell-compartments-and-membrane-surfaces-in-arabidopsis-thaliana
#3
Safira Attacha, David Solbach, Krisztina Bela, Anna Moseler, Stephan Wagner, Markus Schwarzländer, Isabel Aller, Stefanie J Müller, Andreas J Meyer
Glutathione peroxidase-like enzymes (GPXLs) constitute a family of eight peroxidases in Arabidopsis thaliana. In contrast to the eponymous selenocysteine glutathione peroxidases (GPXs) in mammalian cells which use glutathione as electron donor, GPXLs rely on cysteine instead of selenocysteine for activity and depend on the thioredoxin system for reduction. Although plant GPXLs have been implicated in important agronomic traits such as drought tolerance, photooxidative tolerance and immune responses there remain major ambiguities regarding their subcellular localization...
January 19, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28102838/autophagy-dysregulation-in-danon-disease
#4
Anna Chiara Nascimbeni, Marina Fanin, Corrado Angelini, Marco Sandri
The autophagy-lysosome system is critical for muscle homeostasis and defects in lysosomal function result in a number of inherited muscle diseases, generally referred to as autophagic vacuolar myopathies (AVMs). Among them, Danon Disease (DD) and glycogen storage disease type II (GSDII) are due to primary lysosomal protein defects. DD is characterized by mutations in the lysosome-associated membrane protein 2 (LAMP2) gene. The DD mouse model suggests that inefficient lysosome biogenesis/maturation and impairment of autophagosome-lysosome fusion contribute to the pathogenesis of muscle wasting...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102191/a-broadly-protective-therapeutic-antibody-against-influenza-b-virus-with-two-mechanisms-of-action
#5
Ning Chai, Lee R Swem, Summer Park, Gerald Nakamura, Nancy Chiang, Alberto Estevez, Rina Fong, Lynn Kamen, Elviza Kho, Mike Reichelt, Zhonghua Lin, Henry Chiu, Elizabeth Skippington, Zora Modrusan, Jeremy Stinson, Min Xu, Patrick Lupardus, Claudio Ciferri, Man-Wah Tan
Influenza B virus (IBV) causes annual influenza epidemics around the world. Here we use an in vivo plasmablast enrichment technique to isolate a human monoclonal antibody, 46B8 that neutralizes all IBVs tested in vitro and protects mice against lethal challenge of all IBVs tested when administered 72 h post infection. 46B8 demonstrates a superior therapeutic benefit over Tamiflu and has an additive antiviral effect in combination with Tamiflu. 46B8 binds to a conserved epitope in the vestigial esterase domain of hemagglutinin (HA) and blocks HA-mediated membrane fusion...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28102001/evaluation-of-the-hybrid-resolution-pace-model-for-the-study-of-folding-insertion-and-pore-formation-of-membrane-associated-peptides
#6
Michael D Ward, Shivangi Nangia, Eric R May
The PACE force field presents an attractive model for conducting molecular dynamics simulations of membrane-protein systems. PACE is a hybrid model, in which lipids and solvents are coarse-grained consistent with the MARTINI mapping, while proteins are described by a united atom model. However, given PACE is linked to MARTINI, which is widely used to study membranes, the behavior of proteins interacting with membranes has only been limitedly examined in PACE. In this study, PACE is used to examine the behavior of several peptides in membrane environments, namely WALP peptides, melittin and influenza hemagglutinin fusion peptide (HAfp)...
January 19, 2017: Journal of Computational Chemistry
https://www.readbyqxmd.com/read/28100639/munc13-4-functions-as-a-ca2-sensor-for-homotypic-secretory-granule-fusion-to-generate-endosomal-exocytic-vacuoles
#7
Sang Su Woo, Declan J James, Thomas F J Martin
Munc13-4 is a Ca(2+)-dependent SNARE- and phospholipid-binding protein that localizes to and primes secretory granules (SGs) for Ca(2+)-evoked secretion in various secretory cells. Studies in mast cell-like RBL-2H3 cells provides direct evidence that Munc13-4 with its two Ca(2+)-binding C2 domains functions as a Ca(2+) sensor for SG exocytosis. Unexpectedly, Ca(2+) stimulation also generated large (>2.4 μm diameter) Munc13-4(+)/Rab7(+)/Rab11(+) endosomal vacuoles. Vacuole generation involved the homotypic fusion of Munc13-4(+)/Rab7(+) SGs followed by a merge with Rab11(+) endosomes, and depended on Ca(2+) binding to Munc13-4...
January 18, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28100638/retromer-driven-membrane-tubulation-separates-endosomal-recycling-from-rab7-ypt7-dependent-fusion
#8
Latha Kallur Purushothaman, Henning Arlt, Anne Kuhlee, Stefan Raunser, Christian Ungermann
Endosomes are the major protein sorting hubs of the endocytic pathway. They sort proteins destined for degradation into internal vesicles, while in parallel recycling receptors via tubular carriers back to the Golgi. Tubule formation depends on the Rab7/Ypt7-interacting retromer complex, consisting of the sorting nexin dimer (SNX-BAR) and the trimeric cargo selection complex (CSC). Fusion of mature endosomes with the lysosome-like vacuole also requires Rab7/Ypt7. Here, we now solved a major problem in understanding this dual function of endosomal Rab7/Ypt7 using a fully reconstituted system, including purified, full-length yeast SNX-BAR and CSC, whose overall structure we present...
January 18, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28100610/the-measles-virus-receptor-slamf1-can-mediate-particle-endocytosis
#9
Daniel Gonçalves-Carneiro, Jane A McKeating, Dalan Bailey
: The signalling lymphocyte activation molecule F1 (SLAMF1) is both a microbial sensor and entry receptor for Measles virus (MeV). Herein, we describe a new role for SLAMF1 to mediate MeV endocytosis that is in contrast with the alternative, and generally accepted, model that MeV genome enters cells only after fusion at the cell surface. We demonstrated that MeV engagement of SLAMF1 induces dramatic but transient morphological changes, most prominently in the formation of membrane blebs, which were shown to co-localise with incoming viral particles, and rearrangement of the actin cytoskeleton in infected cells...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28097727/energetics-kinetics-and-pathway-of-snare-folding-and-assembly-revealed-by-optical-tweezers
#10
REVIEW
Yongli Zhang
Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are universal molecular engines that drive membrane fusion. Particularly, synaptic SNAREs mediate fast calcium-triggered fusion of neurotransmitter-containing vesicles with plasma membranes for synaptic transmission, the basis of all thought and action. During membrane fusion, complementary SNAREs located on two apposed membranes (often called t- and v-SNAREs) join together to assemble into a parallel four-helix bundle, releasing the energy to overcome the energy barrier for fusion...
January 18, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28095880/high-throughput-expression-of-animal-venom-toxins-in-escherichia-coli-to-generate-a-large-library-of-oxidized-disulphide-reticulated-peptides-for-drug-discovery
#11
Jeremy Turchetto, Ana Filipa Sequeira, Laurie Ramond, Fanny Peysson, Joana L A Brás, Natalie J Saez, Yoan Duhoo, Marilyne Blémont, Catarina I P D Guerreiro, Loic Quinton, Edwin De Pauw, Nicolas Gilles, Hervé Darbon, Carlos M G A Fontes, Renaud Vincentelli
BACKGROUND: Animal venoms are complex molecular cocktails containing a wide range of biologically active disulphide-reticulated peptides that target, with high selectivity and efficacy, a variety of membrane receptors. Disulphide-reticulated peptides have evolved to display improved specificity, low immunogenicity and to show much higher resistance to degradation than linear peptides. These properties make venom peptides attractive candidates for drug development. However, recombinant expression of reticulated peptides containing disulphide bonds is challenging, especially when associated with the production of large libraries of bioactive molecules for drug screening...
January 17, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28089882/a-highly-efficient-modified-human-serum-albumin-signal-peptide-to-secrete-proteins-in-cells-derived-from-different-mammalian-species
#12
Carolina Attallah, Marina Etcheverrigaray, Ricardo Kratje, Marcos Oggero
Signal peptides (SPs) are key elements in the production of recombinant proteins; however, little information is available concerning different SP in mammalian cells other than CHO. In order to study the efficiency of different SPs to direct the traffic along the secretory pathway of the green fluorescence protein (GFP) and a scFv-Fc fusion protein; CHO-K1, HEK293 and NS0 cell lines were transfected in a transient and stable way. SP of human azurocidin (AZ), modified human albumin (mSA), modified Cricetulus griseus Ig kappa chain V III region MOPC 63 like (mIgκ C) and modified human Ig kappa chain V III region VG (mIgκ H) were evaluated...
January 10, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28089515/navigation-through-the-plasma-membrane-molecular-landscape-shapes-random-organelle-movement
#13
Alison R Dun, Gabriel J Lord, Rhodri S Wilson, Deirdre M Kavanagh, Katarzyna I Cialowicz, Shuzo Sugita, Seungmee Park, Lei Yang, Annya M Smyth, Andreas Papadopulos, Colin Rickman, Rory R Duncan
Eukaryotic plasma membrane organization theory has long been controversial, in part due to a dearth of suitably high-resolution techniques to probe molecular architecture in situ and integrate information from diverse data streams [1]. Notably, clustered patterning of membrane proteins is a commonly conserved feature across diverse protein families (reviewed in [2]), including the SNAREs [3], SM proteins [4, 5], ion channels [6, 7], and receptors (e.g., [8]). Much effort has gone into analyzing the behavior of secretory organelles [9-13], and understanding the relationship between the membrane and proximal organelles [4, 5, 12, 14] is an essential goal for cell biology as broad concepts or rules may be established...
January 9, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28088448/fast-formation-of-low-defect-density-tethered-bilayers-by-fusion-of-multilamellar-vesicles
#14
Tadas Ragaliauskas, Mindaugas Mickevicius, Bozena Rakovska, Tadas Penkauskas, David J Vanderah, Frank Heinrich, Gintaras Valincius
A facile and reproducible preparation of surface-supported lipid bilayers is essential for fundamental membrane research and biotechnological applications. We demonstrate that multilamellar vesicles fuse to molecular-anchor-grafted surfaces yielding low-defect-density, tethered bilayer membranes. Continuous bilayers are formed within 10min, while the electrically insulating bilayers with <0.1μm(-2) defect density can be accomplished within 60min. Surface plasmon resonance spectroscopy indicates that an amount of lipid material transferred from vesicles to a surface is inversely proportional to the density of an anchor, while the total amount of lipid that includes tethered and transferred lipid remains constant within 5% standard error...
January 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28087229/disease-associated-mutations-identify-a-novel-region-in-human-sting-necessary-for-the-control-of-type-i-interferon-signaling
#15
Isabelle Melki, Yoann Rose, Carolina Uggenti, Lien Van Eyck, Marie-Louise Frémond, Naoki Kitabayashi, Gillian I Rice, Emma M Jenkinson, Anaïs Boulai, Nadia Jeremiah, Marco Gattorno, Sefano Volpi, Olivero Sacco, Suzanne W J Terheggen-Lagro, Harm A W M Tiddens, Isabelle Meyts, Marie-Anne Morren, Petra De Haes, Carine Wouters, Eric Legius, Anniek Corveleyn, Frederic Rieux-Laucat, Christine Bodemer, Isabelle Callebaut, Mathieu P Rodero, Yanick J Crow
BACKGROUND: Gain-of-function mutations in transmembrane protein 173 (TMEM173) encoding stimulator of interferon genes (STING) underlie a recently described type I interferonopathy called STING-associated vasculopathy with onset in infancy (SAVI). OBJECTIVES: We sought to define the molecular and cellular pathology relating to 3 individuals variably exhibiting the core features of the SAVI phenotype including systemic inflammation, destructive skin lesions, and interstitial lung disease...
January 3, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28078583/generation-and-application-of-bioluminescent-cd95-ligand-fusion-proteins
#16
Isabell Lang, Juliane Kums, Harald Wajant
The quantitative evaluation of the interaction of soluble CD95L with CD95 is not only important for a detailed understanding of CD95 biology but is also of special relevance for the characterization and development of inhibitors of this interaction. The assembly of a CD95L-CD95 complex capable to recruit intracellular factors not only involves pre-assembly of CD95 molecules in the absence of CD95L but is also modulated by cellular factors such as interaction with the actin cytoskeleton and plasma membrane compartmentation of CD95...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28077717/complexin-mutants-reveal-partial-segregation-between-recycling-pathways-that-drive-evoked-and-spontaneous-neurotransmission
#17
Nadezhda Sabeva, Richard W Cho, Alexander Vasin, Agustin Gonzalez, J Troy Littleton, Maria Bykhovskaia
: Synaptic vesicles fuse at morphological specializations in the presynaptic terminal termed active zones (AZs). Vesicle fusion can occur spontaneously or in response to an action potential. Following fusion, vesicles are retrieved and recycled within nerve terminals. It is still unclear whether vesicles that fuse spontaneously or following evoked release share similar recycling mechanisms. Genetic deletion of the SNARE-binding protein complexin dramatically increases spontaneous fusion, with the protein serving as the synaptic vesicle fusion clamp at Drosophila synapses...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28077293/autophagosome-maturation-and-fusion
#18
REVIEW
Fulvio Reggiori, Christian Ungermann
Macroautophagy or simply autophagy, is a degradative pathway that delivers cytoplasmic components, including cytosol and organelles, to the lysosome in double-membrane vesicles called autophagosomes. This process is initiated at the pre-autophagosomal structure or phagophore assembly site (PAS), and involves a number of highly conserved autophagy-related (Atg) proteins. Those support the generation and conversion of an open membranous cistern known as the phagophore or isolation membrane, into a closed autophagosome...
January 8, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28076803/drunken-membranes-short-chain-alcohols-alter-fusion-of-liposomes-to-planar-lipid-bilayers
#19
Jason Paxman, Brady Hunt, David Hallan, Samuel R Zarbock, Dixon J Woodbury
Although the effects of ethanol on protein receptors and lipid membranes have been studied extensively, ethanol's effect on vesicles fusing to lipid bilayers is not known. To determine the effect of alcohols on fusion rates, we utilized the nystatin/ergosterol fusion assay to measure fusion of liposomes to a planar lipid bilayer (BLM). The addition of ethanol excited fusion when applied on the cis (vesicle) side, and inhibited fusion on the trans side. Other short-chain alcohols followed a similar pattern. In general, the inhibitory effect of alcohols (trans) occurs at lower doses than the excitatory (cis) effect, with a decrease of 29% in fusion rates at the legal driving limit of 0...
January 10, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28076385/the-effect-of-a-novel-c-820c-t-arg274trp-mutation-in-the-mitofusin-2-gene-on-fibroblast-metabolism-and-clinical-manifestation-in-a-patient
#20
Małgorzata Beręsewicz, Anna Boratyńska-Jasińska, Łukasz Charzewski, Maria Kawalec, Dagmara Kabzińska, Andrzej Kochański, Krystiana A Krzyśko, Barbara Zabłocka
Charcot-Marie-Tooth disease type 2A (CMT2A) is an autosomal dominant axonal peripheral neuropathy caused by mutations in the mitofusin 2 gene (MFN2). Mitofusin 2 is a GTPase protein present in the outer mitochondrial membrane and responsible for regulation of mitochondrial network architecture via the fusion of mitochondria. As that fusion process is known to be strongly dependent on the GTPase activity of mitofusin 2, it is postulated that the MFN2 mutation within the GTPase domain may lead to impaired GTPase activity, and in turn to mitochondrial dysfunction...
2017: PloS One
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