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https://www.readbyqxmd.com/read/28538731/a-neural-circuit-architecture-for-angular-integration-in-drosophila
#1
Jonathan Green, Atsuko Adachi, Kunal K Shah, Jonathan D Hirokawa, Pablo S Magani, Gaby Maimon
Many animals keep track of their angular heading over time while navigating through their environment. However, a neural-circuit architecture for computing heading has not been experimentally defined in any species. Here we describe a set of clockwise- and anticlockwise-shifting neurons in the Drosophila central complex whose wiring and physiology provide a means to rotate an angular heading estimate based on the fly's angular velocity. We show that each class of shifting neurons exists in two subtypes, with spatiotemporal activity profiles that suggest different roles for each subtype at the start and end of tethered-walking turns...
May 22, 2017: Nature
https://www.readbyqxmd.com/read/28530653/structure-of-a-pre-catalytic-spliceosome
#2
Clemens Plaschka, Pei-Chun Lin, Kiyoshi Nagai
Intron removal requires assembly of the spliceosome on pre-mRNA and extensive remodelling to form the spliceosome's catalytic centre. Here we report the cryo-electron microscopy structure of the yeast pre-catalytic B complex spliceosome at near-atomic resolution. The mobile U2 snRNP associates with U4/U6.U5 tri-snRNP through U2/U6 helix II and an interface between U4/U6 di-snRNP and the U2 snRNP SF3b-containing domain, which also transiently contacts the helicase Brr2. The U2 snRNP 3' region is flexibly attached to the SF3b-containing domain and protrudes over the concave surface of tri-snRNP, where the U1 snRNP may reside before its release from the pre-mRNA 5'-splice site...
May 22, 2017: Nature
https://www.readbyqxmd.com/read/28528970/the-many-faces-of-compartmentalized-pka-signalosomes
#3
REVIEW
Omar Torres-Quesada, Johanna E Mayrhofer, Eduard Stefan
Cellular signal transmission requires the dynamic formation of spatiotemporally controlled molecular interactions. At the cell surface information is received by receptor complexes and relayed through intracellular signaling platforms which organize the actions of functionally interacting signaling enzymes and substrates. The list of hormone or neurotransmitter pathways that utilize the ubiquitous cAMP-sensing protein kinase A (PKA) system is expansive. This requires that the specificity, duration, and intensity of PKA responses are spatially and temporally restricted...
May 18, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28528437/initial-contact-the-first-steps-in-herpesvirus-entry
#4
Walid Azab, Klaus Osterrieder
The entry process of herpesviruses into host cells is complex and highly variable. It involves a sequence of well-orchestrated events that begin with virus attachment to glycan-containing proteinaceous structures on the cell surface. This initial contact tethers virus particles to the cell surface and results in a cascade of molecular interactions, including the tight interaction of viral envelope glycoproteins to specific cell receptors. These interactions trigger intracellular signaling and finally virus penetration after fusion of the viral envelope with cellular membranes...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28523855/double-activation-catalysis-for-%C3%AE-%C3%A2-alkylidene-cyclic-enones-with-chiral-amines-and-thiols
#5
Ying-Chun Chen, Zhou-Xiang Wang, Zhi Zhou, Wei Xiao, Qin Ouyang, Wei Du
Cooperative catalysis has contributed greatly to the progress of asymmetric synthesis. Nevertheless, the double activation catalysis has been less explored, especially in a covalently tethered pattern. Here we present a double activation strategy for α´-alkylidene cyclic enone substrates with a chiral primary amine and 2-mercaptobenzoic acid, through regio- and chemoselective additions to generate the complex interrupted iminium ion species. Significantly enhanced reactivity and enantioselectivity have been observed in the β-regioselective Michael addition and Friedel-Crafts alkylation reactions with malononitriles and indoles, respectively, producing a spectrum of chiral cyclic adducts with an exo-alkylidene group...
May 18, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28521960/yeast-dynamin-associates-with-the-garp-tethering-complex-for-endosome-to-golgi-traffic
#6
Uma Saimani, Jared Smothers, Hyoeun McDermott, Pelin Makaraci, Kyoungtae Kim
Yeast dynamin, Vacuolar Protein Sorting 1 (Vps1), has been implicated in recycling traffic from the endosome to the trans-Golgi network (TGN). Previous research showed a genetic interaction of Vps1 with all components of the GARP tethering complex, which anchors vesicles at the late Golgi membrane. We used the yeast two-hybrid system and have identified a 33 amino acid segment of Vps51, a GARP subunit, that interacts with Vps1. Based on sequence homology between Vps51 and its mammalian homolog Ang2 in the 33 amino acids stretch, we identified two key residues of Vps51, E127 and Y129, that bind Vps1...
May 8, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28520978/ldb1-mediated-enhancer-looping-can-be-established-independent-of-mediator-and-cohesin
#7
Ivan Krivega, Ann Dean
Mechanistic studies in erythroid cells indicate that LDB1, as part of a GATA1/TAL1/LMO2 complex, brings erythroid-expressed genes into proximity with enhancers for transcription activation. The role of co-activators in establishing this long-range interaction is poorly understood. Here we tested the contributions of the RNA Pol II pre-initiation complex (PIC), mediator and cohesin to establishment of locus control region (LCR)/β-globin proximity. CRISPR/Cas9 editing of the β-globin promoter to eliminate the RNA Pol II PIC by deleting the TATA-box resulted in loss of transcription, but enhancer-promoter interaction was unaffected...
May 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28515678/soluble-ectodomain-of-neuroligin-1-decreases-synaptic-activity-by-activating-metabotropic-glutamate-receptor-2
#8
Michelle D Gjørlund, Eva M M Carlsen, Andreas B Kønig, Oksana Dmytrieva, Anders V Petersen, Jacob Jacobsen, Vladimir Berezin, Jean-François Perrier, Sylwia Owczarek
Synaptic cell adhesion molecules represent important targets for neuronal activity-dependent proteolysis. Postsynaptic neuroligins (NLs) form trans-synaptic complexes with presynaptic neurexins (NXs). Both NXs and NLs are cleaved from the cell surface by metalloproteases in an activity-dependent manner, releasing a soluble extracellular fragment and membrane-tethered C-terminal fragment. The cleavage of NL1 depresses synaptic transmission, but the mechanism by which this occurs is unknown. Metabotropic glutamate receptor 2 (mGluR2) are located primarily at the periphery of presynaptic terminals, where they inhibit the formation of cyclic adenosine monophosphate (cAMP) and consequently suppress the release of glutamate and decrease synaptic transmission...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28514856/cell-adhesion-on-rgd-displaying-knottins-with-varying-numbers-of-tryptophan-amino-acids-to-tune-the-affinity-for-assembly-on-cucurbit-8-uril-surfaces
#9
Shrikrishnan Sankaran, Emanuela Cavatorta, Jurriaan Huskens, Pascal Jonkheijm
Cell adhesion is studied on multivalent knottins, displaying RGD ligands with a high affinity for integrin receptors, that are assembled on CB[8]-methylviologen-modified surfaces. The multivalency in the knottins stems from the number of tryptophan amino acid moieties, between 0 and 4, that can form a heteroternary complex with cucurbit[8]uril (CB[8]) and surface-tethered methylviologen (MV(2+)). The binding affinity of the knottins with CB[8] and MV(2+) surfaces was evaluated using surface plasmon resonance spectroscopy...
May 25, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28513583/the-cohesin-like-recn-protein-stimulates-reca-mediated-recombinational-repair-of-dna-double-strand-breaks
#10
Lee A Uranga, Emigdio D Reyes, Praveen L Patidar, Lindsay N Redman, Shelley L Lusetti
RecN is a cohesin-like protein involved in DNA double-strand break repair in bacteria. The RecA recombinase functions to mediate repair via homologous DNA strand invasion to form D-loops. Here we provide evidence that the RecN protein stimulates the DNA strand invasion step of RecA-mediated recombinational DNA repair. The intermolecular DNA tethering activity of RecN protein described previously cannot fully explain this novel activity since stimulation of RecA function is species-specific and requires RecN ATP hydrolysis...
May 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28508654/asymmetric-transfer-hydrogenation-of-1-3-alkoxy-aryloxy-propanones-using-tethered-arene-ru-ii-tsdpen-complexes
#11
Sam Forshaw, Alexander J Matthews, Thomas J Brown, Louis J Diorazio, Luke Williams, Martin Wills
A series of propanones containing combinations of aryloxy and alkoxy substituents at the 1- and 3-positions were reduced to the alcohols via asymmetric transfer hydrogenation using a tethered Ru(II)/TsDPEN catalyst. The enantioselectivities of the reductions reveal a complex pattern of electronic and steric effects which, when used in a matched combination, can lead to the formation of products of up to 68% ee (84:16 er) from this highly challenging class of substrate.
May 16, 2017: Organic Letters
https://www.readbyqxmd.com/read/28507706/ph-and-ligand-induced-release-of-loads-from-dna-acrylamide-hydrogel-microcapsules
#12
Wei-Ching Liao, Sivan Lilienthal, Jason S Kahn, Marianna Riutin, Yang Sung Sohn, Rachel Nechushtai, Itamar Willner
Herein, a method to construct stimuli-responsive DNA-acrylamide-based hydrogel microcapsules has been presented. This method involves the use of polyacrylamide chains modified with predesigned nucleic acid hairpin units and optionally single-strand tethers that provide the required hybridization and recognition functions to yield substrate-loaded stimuli-responsive hydrogel-based microcapsules. The synthesis of the microcapsules involves the loading of CaCO3 microparticles with the respective load substrates and the functionalization of the CaCO3 template particles with nucleic acid promoter units...
May 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28506890/biomechanics-of-the-transport-barrier-in-the-nuclear-pore-complex
#13
REVIEW
George J Stanley, Ariberto Fassati, Bart W Hoogenboom
The nuclear pore complex (NPC) is the selective gateway through which all molecules must pass when entering or exiting the nucleus. It is a cog in the gene expression pathway, an entrance to the nucleus exploited by viruses, and a highly-tuned nanoscale filter. The NPC is a large proteinaceous assembly with a central lumen occluded by natively disordered proteins, known as FG-nucleoporins (or FG-nups). These FG-nups, along with a family of soluble proteins known as nuclear transport receptors (NTRs), form the selective transport barrier...
May 12, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28505407/unique-n-phenylacetylation-and-nrps-with-substrate-promiscuity-for-biosynthesis-of-heptapeptide-variants-jbir-78-and-jbir-95
#14
Kunpei Takeda, Kohei Kemmoku, Yasuharu Satoh, Yasushi Ogasawara, Kazuo Shin-Ya, Tohru Dairi
JBIR-78 (1) and JBIR-95 (2), both of which are heptapeptide derivatives isolated from Kibdelosporangium sp. AK-AA56, have the same amino acid sequences except for the second amino acid; phenylacetic acid (Paa)-L-Val-D-Asp (1)/D-cysteic acid (2)-L-Ala-(3S)-3-hydroxy-D-Leu-Gly-D-Ala-L-Phe. Heterologous expression of the biosynthetic gene cluster including genes encoding non-ribosomal peptide synthetases (NRPS) and in vitro assays with recombinant Orf3, L-cysteic acid synthase homolog, suggested the single A-domain in module 2 activates both L-Asp and L-cysteic acid to yield 1 and 2, respectively, although the substrate specificities of the A-domains of NRPSs are usually strict...
May 15, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28500527/ftsz-ring-architecture-and-its-control-by-mincd
#15
Piotr Szwedziak, Debnath Ghosal
In bacteria and archaea, the most widespread cell division system is based on the tubulin homologue FtsZ protein, whose filaments form the cytokinetic Z-ring. FtsZ filaments are tethered to the membrane by anchors such as FtsA and SepF and are regulated by accessory proteins. One such set of proteins is responsible for Z-ring's spatiotemporal regulation, essential for the production of two equal-sized daughter cells. Here, we describe how our still partial understanding of the FtsZ-based cell division process has been progressed by visualising near-atomic structures of Z-rings and complexes that control Z-ring positioning in cells, most notably the MinCDE and Noc systems that act by negatively regulating FtsZ filaments...
2017: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/28500522/e-coli-cell-cycle-machinery
#16
Joe Lutkenhaus, Shishen Du
Cytokinesis in E. coli is organized by a cytoskeletal element designated the Z ring. The Z ring is formed at midcell by the coalescence of FtsZ filaments tethered to the membrane by interaction of FtsZ's conserved C-terminal peptide (CCTP) with two membrane-associated proteins, FtsA and ZipA. Although interaction between an FtsZ monomer and either of these proteins is of low affinity, high affinity is achieved through avidity - polymerization linked CCTPs interacting with the membrane tethers. The placement of the Z ring at midcell is ensured by antagonists of FtsZ polymerization that are positioned within the cell and target FtsZ filaments through the CCTP...
2017: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/28490657/targeting-endogenous-proteins-for-degradation-through-the-affinity-directed-protein-missile-system
#17
Luke J Fulcher, Luke D Hutchinson, Thomas J Macartney, Craig Turnbull, Gopal P Sapkota
Targeted proteolysis of endogenous proteins is desirable as a research toolkit and in therapeutics. CRISPR/Cas9-mediated gene knockouts are irreversible and often not feasible for many genes. Similarly, RNA interference approaches necessitate prolonged treatments, can lead to incomplete knockdowns and are often associated with off-target effects. Targeted proteolysis can overcome these limitations. In this report, we describe an affinity-directed protein missile (AdPROM) system that harbours the von Hippel-Lindau (VHL) protein, the substrate receptor of the Cullin2 (CUL2) E3 ligase complex, tethered to polypeptide binders that selectively bind and recruit endogenous target proteins to the CUL2-E3 ligase complex for ubiquitination and proteasomal degradation...
May 2017: Open Biology
https://www.readbyqxmd.com/read/28490590/the-c-terminus-of-the-herpes-simplex-virus-pul25-protein-is-required-for-release-of-viral-genomes-from-capsids-bound-to-nuclear-pores
#18
Jamie B Huffman, Gina R Daniel, Erik Falck-Pedersen, Alexis Huet, Greg A Smith, James F Conway, Fred L Homa
The herpes simplex virus (HSV) capsid is released into the cytoplasm after fusion of viral and host membranes, whereupon dynein-dependent trafficking along microtubules targets it to the nuclear envelope. Binding of the capsid to the nuclear pore complex (NPC) is mediated by the capsid protein pUL25 and the capsid-tethered tegument protein pUL36. Temperature-sensitive mutants in both pUL25 and pUL36 dock at the NPC but fail to release DNA. The uncoating reaction has been difficult to study due to the rapid release of the genome once the capsid interacts with the nuclear pore...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28489961/the-role-of-exo70-in-exocytosis-and-beyond
#19
Yueyao Zhu, Bin Wu, Wei Guo
The exocyst complex mediates the tethering of secretory vesicles to the plasma membrane prior to SNARE-mediated membrane fusion. Recent studies have implicated the exocyst in a wide range of cellular processes. Particularly, research on the Exo70 subunit of the complex has linked the function of the exocyst in exocytosis to cell adhesion, migration and invasion. In this review, we will discuss the recent work on how Exo70 regulates these cellular processes, and how small GTPases and kinases interact with Exo70 to orchestrate its function in exocytosis and cytoskeleton organization...
May 10, 2017: Small GTPases
https://www.readbyqxmd.com/read/28484455/real-time-characterization-of-antibody-binding-to-receptors-on-living-immune-cells
#20
Sina Bondza, Eleanor Foy, Jonathan Brooks, Karl Andersson, James Robinson, Pascale Richalet, Jos Buijs
Understanding molecular interactions on immune cells is crucial for drug development to treat cancer and autoimmune diseases. When characterizing molecular interactions, the use of a relevant living model system is important, as processes such as receptor oligomerization and clustering can influence binding patterns. We developed a protocol to enable time-resolved analysis of ligand binding to receptors on living suspension cells. Different suspension cell lines and weakly adhering cells were tethered to Petri dishes with the help of a biomolecular anchor molecule, and antibody binding was analyzed using LigandTracer...
2017: Frontiers in Immunology
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