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Tethering complex

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https://www.readbyqxmd.com/read/28934205/a-rab5-gtpase-module-is-important-for-autophagosome
#1
Fan Zhou, Shenshen Zou, Yong Chen, Zhanna Lipatova, Dan Sun, Xiaolong Zhu, Rui Li, Zulin Wu, Weiming You, Xiaoxia Cong, Yiting Zhou, Zhiping Xie, Valeriya Gyurkovska, Yutao Liu, Qunli Li, Wenjing Li, Jie Cheng, Yongheng Liang, Nava Segev
In the conserved autophagy pathway, the double-membrane autophagosome (AP) engulfs cellular components to be delivered for degradation in the lysosome. While only sealed AP can productively fuse with the lysosome, the molecular mechanism of AP closure is currently unknown. Rab GTPases, which regulate all intracellular trafficking pathways in eukaryotes, also regulate autophagy. Rabs function in GTPase modules together with their activators and downstream effectors. In yeast, an autophagy-specific Ypt1 GTPase module, together with a set of autophagy-related proteins (Atgs) and a phosphatidylinositol-3-phosphate (PI3P) kinase, regulates AP formation...
September 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28933436/stereodivergent-synthesis-with-a-programmable-molecular-machine
#2
Salma Kassem, Alan T L Lee, David A Leigh, Vanesa Marcos, Leoni I Palmer, Simone Pisano
It has been convincingly argued that molecular machines that manipulate individual atoms, or highly reactive clusters of atoms, with Ångström precision are unlikely to be realized. However, biological molecular machines routinely position rather less reactive substrates in order to direct chemical reaction sequences, from sequence-specific synthesis by the ribosome to polyketide synthases, where tethered molecules are passed from active site to active site in multi-enzyme complexes. Artificial molecular machines have been developed for tasks that include sequence-specific oligomer synthesis and the switching of product chirality, a photo-responsive host molecule has been described that is able to mechanically twist a bound molecular guest, and molecular fragments have been selectively transported in either direction between sites on a molecular platform through a ratchet mechanism...
September 20, 2017: Nature
https://www.readbyqxmd.com/read/28931724/vps18-recruits-vps41-to-the-human-hops-complex-via-a-ring-ring-interaction
#3
Morag Hunter, Edward J Scourfield, Edward Emmott, Stephen C Graham
Eukaryotic cells use conserved multisubunit membrane tethering complexes, including CORVET and HOPS, to control the fusion of endomembranes. These complexes have been extensively studied in yeast, but to date there have been far fewer studies of metazoan CORVET and HOPS. Both of these complexes comprise six subunits: a common four-subunit core and two unique subunits. Once assembled, these complexes function to recognise specific endosomal membrane markers and facilitate SNARE-mediated membrane fusion. CORVET promotes the homotypic fusion of early endosomes, while HOPS promotes the fusion of lysosomes to late endosomes and autophagosomes...
September 20, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28925353/sec17-%C3%AE-snap-and-an-sm-tethering-complex-regulate%C3%A2-the-outcome-of-snare-zippering-in-vitro-and-in-vivo
#4
Matthew L Schwartz, Daniel P Nickerson, Braden T Lobingier, Rachael L Plemel, Mengtong Duan, Cortney G Angers, Michael Zick, Alexey J Merz
Zippering of SNARE complexes spanning docked membranes is essential for most intracellular fusion events. Here we explore how SNARE regulators operate on discrete zippering states. The formation of a metastable trans-complex, catalyzed by HOPS and its SM subunit Vps33, is followed by subsequent zippering transitions that increase the probability of fusion. Operating independently of Sec18 (NSF) catalysis, Sec17 (α-SNAP) either inhibits or stimulates SNARE-mediated fusion. If HOPS or Vps33 are absent, Sec17 inhibits fusion at an early stage...
September 19, 2017: ELife
https://www.readbyqxmd.com/read/28923950/single-molecule-visualization-of-saccharomyces-cerevisiae-leading-strand-synthesis-reveals-dynamic-interaction-between-mtc-and-the-replisome
#5
Jacob S Lewis, Lisanne M Spenkelink, Grant D Schauer, Flynn R Hill, Roxanna E Georgescu, Michael E O'Donnell, Antoine M van Oijen
The replisome, the multiprotein system responsible for genome duplication, is a highly dynamic complex displaying a large number of different enzyme activities. Recently, the Saccharomyces cerevisiae minimal replication reaction has been successfully reconstituted in vitro. This provided an opportunity to uncover the enzymatic activities of many of the components in a eukaryotic system. Their dynamic behavior and interactions in the context of the replisome, however, remain unclear. We use a tethered-bead assay to provide real-time visualization of leading-strand synthesis by the S...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28921684/generation-of-stable-ruthenium-iv-ketimido-complexes-via-oxidative-addition-of-oxime-esters-to-ruthenium-ii-reactivity-studies-based-on-electronic-properties-of-the-ru-n-bond
#6
Takuya Shimbayashi, Kazuhiro Okamoto, Kouichi Ohe
The reaction of an oxime ester with RuX2(PPh3)3 proceeded smoothly at room temperature to afford a stable Ru(IV)-ketimido complex as an oxidative adduct. The structure of the complex was unambiguously determined by X-ray crystallographic analysis, which showed an almost linear Ru-N-C array. The electronic properties of the nitrogen atom were estimated by density functional theory (DFT) calculations, and results suggested the double-bond character of the Ru-N bond. Kinetic studies combined with consideration of the substituent effect on the oxime ester led to proposing the reaction mechanism involving oxidative addition, which could proceed via N,O-chelate coordination to the Ru center prior to N-O bond cleavage...
September 16, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28916655/tethering-il2-to-its-receptor-il2r%C3%AE-enhances-anti-tumor-activity-and-expansion-of-natural-killer-nk92-cells
#7
Youssef Jounaidi, Joseph F Cotten, Keith W Miller, Stuart A Forman
Interleukin-2 (IL2) is an immunostimulatory cytokine for key immune cells including T cells and natural killer (NK) cells. Systemic IL2 supplementation could enhance NK-mediated immunity in a variety of diseases ranging from neoplasms to viral infection. However, its systemic use is restricted by its serious side effects and limited efficacy due to activation of T regulatory cells (Tregs). IL2 signaling is mediated through interactions with a multi-subunit receptor complex containing IL2Rα, IL2Rβ and IL2Rγ...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28914606/nanoscale-architecture-of-the-schizosaccharomyces-pombe-contractile-ring
#8
Nathan A McDonald, Abigail L Lind, Sarah E Smith, Rong Li, Kathleen Gould
The contractile ring is a complex molecular apparatus important for dividing many eukaryotic cells. Despite knowledge of its composition, the molecular architecture of the ring is not known. Here we applied super-resolution microscopy and FRET to determine the nanoscale spatial organization of Schizosaccharomyces pombe contractile ring components relative to the plasma membrane. As in other membrane-tethered actin structures, contractile ring proteins are stratified relative to the membrane. The lowest layer (0-80 nm) contains membrane-binding scaffolds, formin, and the myosin-II tail...
September 15, 2017: ELife
https://www.readbyqxmd.com/read/28911019/early-arabidopsis-root-hair-growth-stimulation-by-pathogenic-strains-of-pseudomonas-syringae
#9
Tamara Pecenková, Martin Janda, Jitka Ortmannová, Vladimíra Hajná, Zuzana Stehlíková, Viktor Žárský
Background and Aims: Selected beneficial Pseudomonas spp. strains have the ability to influence root architecture in Arabidopsis thaliana by inhibiting primary root elongation and promoting lateral root and root hair formation. A crucial role for auxin in this long-term (1week), long-distance plant-microbe interaction has been demonstrated. Methods: Arabidopsis seedlings were cultivated in vitro on vertical plates and inoculated with pathogenic strains Pseudomonas syringae pv...
September 1, 2017: Annals of Botany
https://www.readbyqxmd.com/read/28904204/distinct-roles-of-the-polarity-factors-boi1-and-boi2-in-the-control-of-exocytosis-and-abscission-in-budding-yeast
#10
Aina Masgrau, Andrea Battola, Trinidad Sanmartin, Leszek P Pryszcz, Toni Gabaldón, Manuel Mendoza
Boi1 and Boi2 (Boi1/2) are budding yeast plasma membrane proteins that function in polarized growth, and in cytokinesis inhibition in response to chromosome bridges via the NoCut abscission checkpoint. How Boi1/2 act in these two distinct processes is not understood. We demonstrate that Boi1/2 are required for a late step in the fusion of secretory vesicles with the plasma membrane of the growing bud. Cells lacking Boi1/2 accumulate secretory vesicles and are defective in bud growth. In contrast, Boi2 is specifically required for abscission inhibition in cells with chromatin bridges...
September 13, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28893983/mechanisms-for-restraining-camp-dependent-protein-kinase-revealed-by-subunit-quantitation-and-cross-linking-approaches
#11
Ryan Walker-Gray, Florian Stengel, Matthew G Gold
Protein phosphorylation by cyclic AMP-dependent protein kinase (PKA) underlies key cellular processes, including sympathetic stimulation of heart cells, and potentiation of synaptic strength in neurons. Unrestrained PKA activity is pathological, and an enduring challenge is to understand how the activity of PKA catalytic subunits is directed in cells. We developed a light-activated cross-linking approach to monitor PKA subunit interactions with temporal precision in living cells. This enabled us to refute the recently proposed theory that PKA catalytic subunits remain tethered to regulatory subunits during cAMP elevation...
September 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28889036/multisubunit-tethering-complexes-in-higher-plants
#12
REVIEW
Raksha Ravikumar, Alexander Steiner, Farhah F Assaad
Tethering complexes mediate the initial, specific contact between donor and acceptor membranes. This review focuses on the modularity and function of multisubunit tethering complexes (MTCs) in higher plants. One emphasis is on molecular interactions of plant MTCs. Here, a number of insights have been gained concerning interactions between different tethering complexes, and between tethers and microtubule-associated proteins. The roles of tethering complexes in abiotic stress responses appear indirect, but in the context of biotic stress responses it has been suggested that some tethers are direct targets of pathogen effectors or virulence factors...
September 7, 2017: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/28886335/macromolecular-assemblies-of-the-mammalian-circadian-clock
#13
Rajindra P Aryal, Pieter Bas Kwak, Alfred G Tamayo, Michael Gebert, Po-Lin Chiu, Thomas Walz, Charles J Weitz
The mammalian circadian clock is built on a feedback loop in which PER and CRY proteins repress their own transcription. We found that in mouse liver nuclei all three PERs, both CRYs, and Casein Kinase-1δ (CK1δ) are present together in an ∼1.9-MDa repressor assembly that quantitatively incorporates its CLOCK-BMAL1 transcription factor target. Prior to incorporation, CLOCK-BMAL1 exists in an ∼750-kDa complex. Single-particle electron microscopy (EM) revealed nuclear PER complexes purified from mouse liver to be quasi-spherical ∼40-nm structures...
September 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28883096/cog7-deficiency-in-drosophila-generates-multifaceted-developmental-behavioral-and-protein-glycosylation-phenotypes
#14
Anna Frappaolo, Stefano Sechi, Tadahiro Kumagai, Sarah Robinson, Roberta Fraschini, Angela Karimpour Ghahnavieh, Giorgio Belloni, Roberto Piergentili, Katherine H Tiemeyer, Michael Tiemeyer, Maria Grazia Giansanti
Congenital Disorders of Glycosylation (CDG) comprise a family of human multi-systemic diseases caused by recessive mutations in genes required for protein N-glycosylation. More than 100 distinct forms of CDGs have been identified and most of them cause severe neurological impairment. The Conserved Oligomeric Golgi (COG) complex mediates tethering of vesicles carrying glycosylation enzymes across the Golgi cisternae. Mutations affecting human COG1, COG2, COG4-COG8 cause monogenic forms of inherited, autosomal recessive, CDGs...
September 7, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28883038/yeast-silencing-factor-sir4-and-a-subset-of-nucleoporins-form-a-complex-distinct-from-nuclear-pore-complexes
#15
Diego L Lapetina, Christopher Ptak, Ulyss K Roesner, Richard W Wozniak
Interactions occurring at the nuclear envelope (NE)-chromatin interface influence both NE structure and chromatin organization. Insights into the functions of NE-chromatin interactions have come from the study of yeast subtelomeric chromatin and its association with the NE, including the identification of various proteins necessary for tethering subtelomeric chromatin to the NE and the silencing of resident genes. Here we show that four of these proteins-the silencing factor Sir4, NE-associated Esc1, the SUMO E3 ligase Siz2, and the nuclear pore complex (NPC) protein Nup170-physically and functionally interact with one another and a subset of NPC components (nucleoporins or Nups)...
September 7, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28882044/host-guest-tethered-dna-transducer-atp-fueled-release-of-a-protein-inhibitor-from-cucurbit-7-uril
#16
Xiao Zhou, Xiaoye Su, Pravin Pathak, Ryan Vik, Brittany Vinciguerra, Lyle Isaacs, Janarthanan Jayawickramarajah
Host-guest complexes are emerging as powerful components in functional systems with applications ranging from materials to biomedicine. In particular, CB7 based host-guest complexes have received much attention for the controlled release of drugs due to the remarkable ability of CB7 toward binding input molecules in water with high affinity leading to displacement of CB7 from included pharmacophores (or from drug loaded porous particles). However, the release of bound guests from CB7 in response to endogenous biological molecules remains limited since the input biomolecule needs to have the appropriate chemical structure to bind tightly into the CB7 cavity...
September 7, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28881057/efficient-sensitized-z%C3%A2-e-photoisomerization-of-an-iridium-iii-azobenzene-complex-over-a-wide-concentration-range
#17
Javier Moreno, Lutz Grubert, Jutta Schwarz, David Bléger, Stefan Hecht
To improve the sensitized Z→E photoisomerization of azobenzenes, and circumvent the threshold concentration necessary for the bimolecular photoinduced electron transfer reaction to generate the rapidly isomerizing Z-azobenzene radical anion, an Ir(III) complex with a covalently tethered azobenzene fragment was synthesized. Selective irradiation of the (1) MLCT band of the Ir(III) complex induced an efficiently sensitized photoswitching of the dyad over a wide concentration range and even at high dilution.
September 7, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28880475/recent-new-insights-into-the-role-of-snare-and-associated-proteins-in-insulin-granule-exocytosis
#18
REVIEW
Herbert Y Gaisano
Initial work on the exocytotic machinery of predocked insulin secretory granules (SGs) in pancreatic β-cells mimicked the SNARE hypothesis work in neurons, which includes SM/SNARE complex and associated priming proteins, fusion clamps and Ca(2+) sensors. However, β-cell SGs, unlike neuronal synaptic vesicles, exhibit a biphasic secretory response that requires additional distinct features in exocytosis including newcomer SGs that undergo minimal docking time at the plasma membrane (PM) before fusion and multi-SG (compound) fusion...
September 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28877444/new-tethered-phospholipid-bilayers-integrating-functional-g-protein-coupled-receptor-membrane-proteins
#19
Meriem Chadli, Samuel Rebaud, Ofelia Maniti, Bruno Tillier, Sandra Cortés, Agnès Girard-Egrot
Membrane proteins exhibiting extra- and intracellular domains require an adequate near-native lipid platform for their functional reconstitution. With this aim, we developed a new technology enabling the formation of a peptide-tethered bilayer lipid membrane (pep-tBLM), a lipid bilayer grafted onto peptide spacers, by way of a metal-chelate interaction. To this end, we designed an original peptide spacer derived from the natural α-laminin thiopeptide (P19) possessing a cysteine residue in the N-terminal extremity for grafting onto gold and a C-terminal extremity modified by four histidine residues (P19-4H)...
September 20, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28874828/srsf1-suppresses-selection-of-intron-distal-5-splice-site-of-dok7-intron-4-to-generate-functional-full-length-dok-7-protein
#20
Khalid Bin Ahsan, Akio Masuda, Mohammad Alinoor Rahman, Jun-Ichi Takeda, Mohammad Nazim, Bisei Ohkawara, Mikako Ito, Kinji Ohno
Dok-7 is a non-catalytic adaptor protein that facilitates agrin-induced clustering of acetylcholine receptors (AChR) at the neuromuscular junction. Alternative selection of 5' splice sites (SSs) of DOK7 intron 4 generates canonical and frame-shifted transcripts. We found that the canonical full-length Dok-7 enhanced AChR clustering, whereas the truncated Dok-7 did not. We identified a splicing cis-element close to the 3' end of exon 4 by block-scanning mutagenesis. RNA affinity purification and mass spectrometry revealed that SRSF1 binds to the cis-element...
September 5, 2017: Scientific Reports
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