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Journal of Biological Chemistry

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https://www.readbyqxmd.com/read/30315113/-de-novo-nad-synthesis-is-required-for-intracellular-replication-of-coxiella-burnetii-the-causative-agent-of-the-neglected-zoonotic-disease-q-fever
#1
Mebratu A Bitew, Chen Ai Khoo, Nitika Neha, David P De Souza, Dedreia Tull, Nadeeka K Wawegama, Hayley J Newton, Fiona M Sansom
Coxiella burnetii is an intracellular Gram-negative bacterium responsible for the important zoonotic disease Q fever. Improved genetic tools and the ability to grow this bacterium in host cell-free media has advanced the study of C. burnetii pathogenesis, but the mechanisms that allow it to survive inside the hostile phagolysosome remain incompletely understood. Previous screening of a transposon mutant library for replication within HeLa cells has suggested that nadB , encoding a putative L-aspartate oxidase required for de novo NAD synthesis, is needed for intracellular replication...
October 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30315112/modification-of-auxinic-phenoxyalkanoic-acid-herbicides-by-the-acyl-acid-amido-synthetase-gh3-15-from-arabidopsis
#2
Ashley M Sherp, Soon Goo Lee, Evelyn Schraft, Joseph M Jez
Herbicide-resistance traits are the most widely used agriculture biotechnology products. Yet, to maintain their effectiveness and to mitigate selection of herbicide-resistant weeds, the discovery of new resistance traits that use different chemical modes of action is essential. In plants, the Gretchen Hagen 3 (GH3) acyl acid amido synthetases catalyze the conjugation of amino acids to jasmonate and auxin phytohormones. This reaction chemistry has not been explored as a possible approach for herbicide modification and inactivation...
October 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30315111/electrostatic-repulsion-causes-anticooperative-dna-binding-between-tumor-suppressor-ets-transcription-factors-and-jun-fos-at-composite-dna-sites
#3
Bethany J Madison, Kathleen A Clark, Niraja Bhachech, Peter Hollenhorst, Barbara J Graves, Simon L Currie
Many different transcription factors (TFs) regulate gene expression in a combinatorial fashion, often by binding in close proximity to each other on composite cis-regulatory DNA elements. Here we investigated how ETS TFs bind with the AP1 TFs JUN-FOS at composite DNA-binding sites. DNA-binding ability with JUN-FOS correlated with the phenotype of ETS proteins in prostate cancer. We found that the oncogenic ETS related gene (ERG) and ETS variant (ETV) 1/4/5 subfamilies co-occupy ETS-AP1 sites with JUN-FOS in vitro, whereas JUN-FOS robustly inhibited DNA binding by the tumor suppressors ETS homologous factor (EHF) and SAM pointed domain-containing ETS TF (SPDEF)...
October 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30315110/structural-and-functional-characterization-of-a-modified-legionaminic-acid-involved-in-glycosylation-of-a-bacterial-lipopolysaccharide
#4
Nathan D McDonald, Kristen E DeMeester, Amanda L Lewis, Catherine Leimkuhler Grimes, E Fidelma Boyd
Nonulosonic acids (NulOs) are a diverse family of α-keto acid carbohydrates present across all branches of life. Bacteria biosynthesize NulOs among which are several related prokaryotic-specific isomers and one of which N -acetylneuraminic acid (sialic acid), is common among all vertebrates. Bacteria display various NulO carbohydrates on lipopolysaccharide (LPS), and the identities of these molecules tune host-pathogen recognition mechanisms. The opportunistic bacterial pathogen Vibrio vulnificus possesses the genes for NulO biosynthesis; however, the structures and functions of the V...
October 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30315109/molecular-characterization-of-the-interaction-of-sialic-acid-with-the-periplasmic-binding-protein-from-haemophilus-ducreyi
#5
Thanuja Gangi Setty, Jonathan C Mowers, Aaron G Hobbs, Shubha P Maiya, Sanaa Syed, Robert S Munson, Michael A Apicella, Ramaswamy Subramanian
The primary role of bacterial periplasmic binding proteins is sequestration of essential metabolites present at a low concentration in the periplasm and making them available for active transporters that transfer these ligands into the bacterial cell. The periplasmic binding proteins(SiaP) from the tripartite ATP-independent periplasmic (TRAP) transport system that transports mammalian host-derived sialic acids, have been well studied from different pathogenic bacteria, including Haemophilus influenzae , Fusobacterium nucleatum , Pasteurella multocida , and Vibrio cholerae SiaPs bind the sialic acid N-acetylneuraminic acid (Neu5Ac) with nanomolar affinity by forming electrostatic and hydrogen bonding interactions...
October 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30315108/the-folding-equilibrium-of-huntingtin-exon-1-monomer-depends-on-its-polyglutamine-tract
#6
Jose M Bravo-Arredondo, Natalie C Kegulian, Thomas Schmidt, Nitin K Pandey, Alan J Situ, Tobias S Ulmer, Ralf Langen
Expansion of the polyglutamine (polyQ) tract in exon 1 of the huntingtin protein (Httex1) leads to Huntington's disease resulting in fatal neurodegeneration. However, it remains poorly understood how polyQ expansions alter protein structure and cause toxicity. Using circular dichroism, electron paramagnetic resonance, and NMR spectroscopy, we found here that monomeric Httex1 consists of two co-existing structural states whose ratio is determined by polyQ tract length. We observed that short Q lengths favor a largely random-coil state, whereas long Q lengths increase the proportion of a predominantly α-helical state...
October 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30315107/characterization-of-the-catalytic-flexible-loop-in-the-dihydroorotase-domain-of-the-human-multi-enzymatic-protein-cad
#7
Francisco Del Caño-Ochoa, Araceli Grande-García, María Reverte-López, Marco D'Abramo, Santiago Ramón-Maiques
The dihydroorotase (DHOase) domain of the multifunctional protein carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase (CAD) catalyzes the third step in the de novo biosynthesis of pyrimidine nucleotides in animals. The crystal structure of the DHOase domain of human CAD (huDHOase) revealed that, despite evolutionary divergence, its active site components are highly conserved with those in bacterial DHOases, encoded as monofunctional enzymes. An important element for catalysis, conserved from Escherichia coli to humans, is a flexible loop that closes as a lid over the active site...
October 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30315106/the-mucinous-domain-of-pancreatic-carboxyl-ester-lipase-cel-contains-core-1-core-2-o-glycans-that-can-be-modified-by-abo-blood-group-determinants
#8
Khadija El Jellas, Bente B Johansson, Karianne Fjeld, Aristotelis Antonopoulos, Heike Immervoll, Man H Choi, Dag Hoem, Mark E Lowe, Dominique Lombardo, Pål R Njølstad, Anne Dell, Eric Mas, Stuart M Haslam, Anders Molven
Carboxyl-ester lipase (CEL) is a pancreatic fat-digesting enzyme associated with human disease. Rare mutations in the CEL gene cause a syndrome of pancreatic exocrine and endocrine dysfunction denoted MODY8, whereas a recombined CEL allele increases the risk for chronic pancreatitis. Moreover, CEL has been linked to pancreatic ductal adenocarcinoma (PDAC) through a postulated oncofetal CEL variant termed feto-acinar pancreatic protein (FAPP). The monoclonal antibody mAb16D10 was previously reported to detect a glycotope in the highly O-glycosylated, mucin-like C-terminus of CEL/FAPP...
October 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30315105/transcriptional-repressor-gata-binding-1-mediated-repression-of-sry-box-2-expression-suppresses-cancer-stem-cell-functions-and-tumor-initiation
#9
Xue Gong, Weiguang Liu, Lele Wu, Zhifang Ma, Yuzhi Wang, Shiyi Yu, Jun Zhang, Hao Xie, Guanyun Wei, Fei Ma, Ling Lu, Liming Chen
Cancer stem cells (CSCs) have been reported in a variety of cancers. SRY-box 2 (SOX2) is a member of the SOX family of transcription factors and has been shown to play a critical role in maintaining the functions of CSCs and promoting tumor initiation. However, the underlying mechanisms for the transcriptional regulation of the SOX2 gene in CSCs are unclear. In this study, using in silico and experimental approaches, we identified transcriptional repressor GATA binding 1 (TRPS1), an atypical GATA-type transcription factor, as a critical transcriptional regulator that represses SOX2 expression and thereby suppresses cancer stemness and tumorigenesis...
October 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30315104/5-diphosphoinositol-pentakisphosphate-5-ip-7-regulates-phosphate-release-from-acidocalcisomes-and-yeast-vacuoles
#10
Evgeniy Potapenko, Ciro D Cordeiro, Guozhong Huang, Melissa Storey, Christopher Wittwer, Amit K Dutta, Henning J Jessen, Vincent J Starai, Roberto Docampo
Acidocalcisomes of Trypanosoma brucei and the acidocalcisome-like vacuoles of Saccharomyces cerevisiae are acidic calcium compartments that store polyphosphate (polyP). Both organelles possess a phosphate sodium symporter (TbPho91, and Pho91p, in T. brucei and yeast, respectively), but the roles of these transporters in growth and orthophosphate (Pi) transport are unclear. We found here that Tbpho91-/- trypanosomes have a lower growth rate under phosphate starvation, and contain larger acidocalcisomes that have increased Pi content...
October 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30315103/comprehensive-analysis-of-n-glycans-in-igg-purified-from-ferrets-with-or-without-influenza-a-virus-infection
#11
Guozhang Zou, Martina Kosikova, Su-Ryun Kim, Shweta Kotian, Wells W Wu, Rongfong Shen, David N Powers, Cyrus Agarabi, Hang Xie, Tongzhong Ju
Influenza viruses cause contagious respiratory infections resulting in significant economic burdens to communities. Production of influenza-specific immunoglobulins, specifically IgGs, is one of the major protective immune mechanisms against influenza viruses. In humans, N-glycosylation of IgGs plays a critical role in antigen binding and effector functions. The ferret is the most commonly used animal model for studying influenza pathogenesis, virus transmission, and vaccine development, but its IgG structure and functions remain largely undefined...
October 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30315102/identification-of-the-physiological-substrates-of-pdip-a-pancreas-specific-protein-disulfide-isomerase-family-member
#12
Takushi Fujimoto, Orie Nakamura, Michiko Saito, Akio Tsuru, Masaki Matsumoto, Kenji Kohno, Kenji Inaba, Hiroshi Kadokura
About 20 members of the protein disulfide isomerase (PDI) family are present in the endoplasmic reticulum of mammalian cells. They are thought to catalyze thiol-disulfide exchange reactions within secretory or membrane proteins to assist in their folding or to regulate their functions. PDIp is a PDI family member highly expressed in the pancreas and known to bind estrogen in vivo and in vitro However, the physiological functions of PDIp remained unclear. In this study, we set out to identify its physiological substrates...
October 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30315101/yes-associated-protein-yap-and-transcriptional-co-activator-with-pdz-binding-motif-taz-mediate-cell-density-dependent-proinflammatory-responses
#13
Qiong Zhang, Xu Han, Jinfeng Chen, Xiaomei Xie, Jiafeng Xu, Yang Zhao, Jie Shen, Lin Hu, Pinglong Xu, Hai Song, Long Zhang, Bin Zhao, Ying-Jie Wang, Zongping Xia
A proper inflammatory response is critical to the restoration of tissue homeostasis after injury or infection, but how such a response is modulated by the physical properties of the cellular and tissue microenvironment is not fully understood. Here, using H358, HeLa and HEK293T cells, we report that cell density can modulate inflammatory responses through the Hippo signaling pathway. We found that NF-κβ activation through the proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) is not affected by cell density...
October 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30315100/er-stress-is-not-elevated-in-the-5xfad-mouse-model-of-alzheimer-s-disease
#14
Katherine R Sadleir, Jelena Popovic, Robert Vassar
Alzheimer's disease (AD) mouse models that overexpress amyloid precursor protein (APP) and presenilin 1 (PS1) form β-amyloid (Aβ) plaques, a hallmark AD lesion. It has been assumed that the neuroinflammation, synaptic dysfunction, neurodegeneration, and cognitive impairment observed in these mice are caused by cerebral Aβ accumulation. However, it is also possible that accumulation of overexpressed transmembrane proteins APP and PS1 in the endoplasmic reticulum (ER) triggers chronic ER stress and activation of the unfolded protein response (UPR)...
October 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30309986/nrf2-transcriptionally-activates-the-heat-shock-factor-1-promoter-under-oxidative-stress-and-affects-survival-and-migration-potential-of-mcf7-cells
#15
Soumyadip Paul, Suvranil Ghosh, Sukhendu Mandal, Subrata Sau, Mahadeb Pal
Functional up-regulation of heat shock factor 1 (HSF1) activity through different post-translational modifications has been implicated in the survival and proliferation of various cancers. It is increasingly recognized that the HSF1 gene is also up-regulated at the transcriptional level, a phenomenon correlated with poor prognosis for patients with different cancers, including breast cancer. Here, we analyzed the transcriptional up-regulation of HSF1 in human cells upon arsenite- or peroxide-induced oxidative stress...
October 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30309985/dishevelled-enables-casein-kinase-1-mediated-phosphorylation-of-frizzled-6-required-for-cell-membrane-localization
#16
Katerina Strakova, Maria Kowalski-Jahn, Tomas Gybel, Jana Valnohova, Vishnu M Dhople, Jakub Harnoš, Ondrej Bernatik, Ranjani Sri Ganji, Zbynek Zdrahal, Jan Mulder, Cecilia Lindskog, Vítězslav Bryja, Gunnar Schulte
Frizzleds (FZD) are receptors for secreted lipoglycoproteins of the Wingless/Int-1 (WNT) family, initiating an important signal transduction network in multicellular organisms. FZDs are G protein-coupled receptors (GPCRs), which are well known to be regulated by phosphorylation leading to specific downstream signaling or receptor desensitization. The role and underlying mechanisms of FZD phosphorylation remain largely unexplored. Here, we investigated the phosphorylation of human FZD6 Using MS analysis and a phospho-state- and -site-specific antibody, we found that Ser-648, located in the FZD6 C-terminus, is efficiently phosphorylated by casein kinase 1 ε (CK1ε) and that this phosphorylation requires the scaffolding protein Dishevelled (DVL)...
October 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30309984/metabolic-origin-of-the-fused-aminoacyl-trna-synthetase-glutamyl-prolyl-trna-synthetase
#17
Sandeep M Eswarappa, Alka A Potdar, Sarthak Sahoo, Santhosh Sankar, Paul L Fox
About 1 billion years ago, in a single-celled holozoan ancestor of all animals, a gene fusion of two tRNA synthetases formed the bifunctional enzyme, glutamyl-prolyl tRNA synthetase (EPRS). We propose here that a confluence of metabolic, biochemical, and environmental factors contributed to the specific fusion of glutamyl- (ERS) and prolyl- (PRS) tRNA synthetases. To test this idea we developed a mathematical model that centers on the precursor-product relationship of glutamic acid and proline, as well as metabolic constraints on free glutamic acid availability near the time of the fusion event...
October 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30309983/structural-basis-for-targeting-avian-sarcoma-virus-gag-polyprotein-to-the-plasma-membrane-for-virus-assembly
#18
Jiri Vlach, Gunnar N Eastep, Ruba H Ghanam, Susan M Watanabe, Carol Carter, Jamil S Saad
For most retroviruses, including HIV-1, binding of the Gag polyprotein to the plasma membrane (PM) is mediated by interactions between Gag's N-terminal myristoylated matrix (MA) domain and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) in the PM. The Gag protein of avian sarcoma virus (ASV) lacks the N-myristoylation signal but contains structural domains having functions similar to those of HIV-1 Gag. The molecular mechanism by which ASV Gag binds to the PM is incompletely understood. Here, we employed NMR techniques to elucidate the molecular determinants of the membrane-binding domain of ASV MA (MA87) to lipids and liposomes...
October 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30309982/the-matrix-domain-of-the-gag-protein-from-avian-sarcoma-virus-contains-a-pi-4-5-p2-binding-site-that-targets-gag-to-the-cell-periphery
#19
Susan M Watanabe, Gisselle Medina, Gunnar N Eastep, Ruba H Ghanam, Jiri Vlach, Jamil S Saad, Carol Carter
The Gag protein of avian sarcoma virus (ASV) lacks an N-myristoyl (myr) group, but contains structural domains similar to those of HIV-1 Gag. Similarly to HIV-1, ASV Gag accumulates on the plasma membrane (PM) before egress; however, it is unclear whether the phospholipid PI(4,5)P2 binds directly to the matrix (MA) domain of ASV Gag, as is the case for HIV-1 Gag. Moreover, the role of PI(4,5)P2 in ASV Gag localization and budding has been controversial. Here, we report that substitution of residues that define the PI(4,5)P2-binding site in the ASV MA domain (reported in a companion manuscript), interfere with Gag localization to the cell periphery and inhibit the production of virus-like particles (VLPs)...
October 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30305398/depletion-of-plasma-membrane-associated-phosphoinositides-mimics-inhibition-of-trpm7-channels-by-cytosolic-mg-2-spermine-and-ph
#20
Tetyana Zhelay, Krystyna B Wieczerzak, Pavani Beesetty, Gerald M Alter, Masayuki Matsushita, J Ashot Kozak
Transient receptor potential cation channel subfamily M member 7 (TRPM7) is an ion channel/protein kinase belonging to the TRP melastatin and eEF2 kinase families.  Under physiological conditions, most native TRPM7 channels are inhibited by cytoplasmic Mg2+ , protons and polyamines.  Currents through these channels (ITRPM7 ) are robustly potentiated when the cell interior is exchanged with low Mg2+ -containing buffers.  ITRPM7 is also potentiated by phosphatidyl inositol bisphosphate (PI(4,5)P2 ) and suppressed by its hydrolysis...
October 10, 2018: Journal of Biological Chemistry
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