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Journal of Biological Chemistry

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https://www.readbyqxmd.com/read/29233891/the-ftslb-sub-complex-of-the-bacterial-divisome-is-tetramer-with-an-uninterrupted-ftsl-helix-linking-the-transmembrane-and-periplasmic-regions
#1
Samson G F Condon, Deena-Al Mahbuba, Claire R Armstrong, Gladys Díaz-Vázquez, Samuel J Craven, Loren M LaPointe, Ambalika S Khadria, Rahul Chadda, John A Crooks, Nambirajan Rangarajan, Douglas B Weibel, Aaron A Hoskins, Janice L Robertson, Qiang Cui, Alessandro Senes
In Escherichia coli, FtsLB plays a central role in the initiation of cell division, possibly transducing a signal that will eventually lead to the activation of peptidoglycan remodeling at the forming septum. The molecular mechanisms by which FtsLB operates in the divisome, however, are not understood. Here we present a structural analysis of the FtsLB complex - performed with biophysical, computational and in vivo methods - that establishes the organization of the transmembrane region and proximal coiled coil of the complex...
December 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29233890/phosphate-pi-regulated-heterodimerization-of-the-high-affinity-sodium-dependent-pi-transporters-pit1-slc20a1-and-pit2-slc20a2-underlies-extracellular-pi-sensing-independently-of-pi-uptake
#2
Nina Bon, Greig Couasnay, Annabelle Bourgine, Sophie Sourice, Sarah Beck-Cormier, Jérôme Guicheux, Laurent Beck
Extracellular phosphate (Pi) can act as a signaling molecule that directly alters gene expression and cellular physiology. The ability of cells or organisms to detect changes in extracellular Pi levels implies the existence of a Pi-sensing mechanism that signals to the body or individual cell. However, unlike in prokaryotes, yeasts, and plants, the molecular players involved in Pi sensing in mammals remain unknown. In this study, we investigated the involvement of the high-affinity, Na-dependent Pi transporters PiT1 and PiT2 in mediating Pi signaling in skeletal cells...
December 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29233889/transcriptionally-inducible-pleckstrin-homology-like-domain-family-a-member-1-attenuates-erbb-receptor-activity-by-inhibiting-receptor-oligomerization
#3
Shigeyuki Magi, Kazunari Iwamoto, Noriko Yumoto, Michio Hiroshima, Takeshi Nagashima, Rieko Ohki, Amaya Garcia-Munoz, Natalia Volinsky, Alexander von Kriegsheim, Yasushi Sako, Koichi Takahashi, Shuhei Kimura, Boris N Kholodenko, Mariko Okada-Hatakeyama
Feedback control is a key mechanism in signal transduction, intimately involved in regulating the outcome of the cellular response. Here we report a novel mechanism by which PHLDA1, Pleckstrin homology-like domain, family A, member 1, negatively regulates ErbB receptor signaling by inhibition of receptor oligomerization. We have found that the ErbB3 ligand, heregulin, induces PHILDA1 expression in MCF-7 cells. Transcriptionally-induced PHLDA1 protein directly binds to ErbB3, while knockdown of PHLDA1 increases complex formation between ErbB3 and ErbB2...
December 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29233888/mitochondrial-energy-generation-disorders-genes-mechanisms-and-clues-to-pathology
#4
Ann E Frazier, David R Thorburn, Alison G Compton
Inherited disorders of oxidative phosphorylation cause the clinically and genetically heterogeneous diseases known as mitochondrial energy generation disorders, or mitochondrial diseases. Over the last three decades, mutations causing these disorders have been identified in almost 290 genes, but many patients still remain without a molecular diagnosis. Moreover, while knowledge of the genetic causes is continually expanding, understanding into how these defects lead to cellular dysfunction and organ pathology is still incomplete...
December 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29233887/st6gal-i-sialyltransferase-promotes-tumor-necrosis-factor-tnf-mediated-cancer-cell-survival-via-sialylation-of-the-tnf-receptor-1-tnfr1-death-receptor
#5
Andrew T Holdbrooks, Colleen M Britain, Susan L Bellis
Activation of the TNFR1 death receptor by TNF induces either cell survival or cell death. However, the mechanisms mediating these distinct outcomes remain poorly understood. In the present study, we report that the ST6Gal-I sialyltransferase, an enzyme upregulated in numerous cancers, sialylates TNFR1, and thereby protects tumor cells from TNF-induced apoptosis. Using pancreatic and ovarian cancer cells with ST6Gal-I knockdown or overexpression, we determined that α2-6 sialylation of TNFR1 had no effect on early TNF-induced signaling events including the rapid activation of NFκB, JNK, ERK, and Akt (occurring within 15m)...
December 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29229781/differential-regulation-of-tlr4-induced-il-10-production-in-b-cells-and-macrophages-reveals-a-novel-role-for-rsk1-and-2-in-b-cells
#6
Ruhcha V Sutavani, Iain R Phair, Rebecca Barker, Alison McFarlane, Natalia Shpiro, Stuart Lang, Andrew Woodland, J Simon C Arthur
Increasing evidence has linked dysregulated IL-10 production by IL-10+ve B cells to autoimmunity, highlighting the importance of improving the understanding of the regulation of IL-10 production in these cells. In both B cells and myeloid cells, IL-10 can be produced in response to Toll-like receptor (TLR) agonists. In macrophages, previous studies have established that mitogen- and stress-activated protein kinases (MSKs) regulate IL-10 production via the phosphorylation of cAMP response element-binding (CREB) protein on the IL-10 promoter...
December 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29229780/cathepsin-d-regulates-cathepsin-b-activation-and-disease-severity-predominantly-in-inflammatory-cells-during-experimental-pancreatitis
#7
Ali A Aghdassi, Daniel S John, Matthias Sendler, F Ulrich Weiss, Thomas Reinheckel, Julia Mayerle, Markus M Lerch
Acute pancreatitis is a complex disorder involving both premature intracellular protease activation and inflammatory cell invasion. An initiating event is the intracellular activation of trypsinogen by cathepsin B (CTSB), which can be induced directly via G-protein-coupled receptors on acinar cells or through inflammatory cells. Here, we studied CTSB regulation by another lysosomal hydrolase, cathepsin D (CTSD), using mice with a complete (CTSD-/-) or pancreas-specific conditional CTSD knockout (KO) (CTSDf/f/p48Cre/+)...
December 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29229779/subtle-changes-at-the-variable-domain-interface-of-the-t-cell-receptor-can-strongly-increase-affinity
#8
Preeti Sharma, David M Kranz
Most affinity maturation campaigns for antibodies and T cell receptors (TCRs) operate on the residues at the binding site, located within the loops known as complementarity determining regions (CDRs). Accordingly, mutations in contact residues or so-called second shell residues that increase affinity are typically identified by directed evolution using combinatorial libraries. Here we used single codon libraries of both CDR and non-CDR residues to generate a deep mutational scan of a human TCR against the cancer antigen MART-1/HLA-A2...
December 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29229778/structural-and-functional-insights-into-the-role-of-bamd-and-bame-within-the-%C3%AE-barrel-assembly-machinery-in-neisseria-gonorrhoeae
#9
Aleksandra E Sikora, Igor H Wierzbicki, Ryszard A Zielke, Rachael F Ryner, Konstantin V Korotkov, Susan K Buchanan, Nicholas Noinaj
The β-barrel assembly machinery (BAM) is a conserved multi-component protein complex responsible for the biogenesis of β-barrel outer membrane proteins (OMPs) in Gram-negative bacteria. Given its role in the production of OMPs for survival and pathogenesis, BAM represents an attractive target for the development of therapeutic interventions including drugs and vaccines against multi-drug resistant bacteria such as Neisseria gonorrhoeae The first structure of BamA, the central component of BAM, was from N...
December 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29229777/crystal-structure-of-the-flif-flig-complex-from-helicobacter-pylori-yields-insight-into-the-assembly-of-the-motor-ms-c-ring-in-the-bacterial-flagellum
#10
Chaolun Xue, Kwok Ho Lam, Huawei Zhang, Kailei Sun, Sai Hang Lee, Xin Chen, Shannon Wing Ngor Au
The bacterial flagellar motor is a self-assembling supramolecular nanodevice. Its spontaneous biosynthesis is initiated by the insertion of the MS ring protein FliF into the inner membrane, followed by attachment of the switch protein FliG. Assembly of this multiprotein complex is tightly regulated to avoid nonspecific aggregation, but the molecular mechanisms governing flagellar assembly are unclear. Here, we present the crystal structure of the cytoplasmic domain of FliF complexed with the N-terminal domain of FliG (FliFC-FliGN) from the bacterium Helicobacter pylori Within this complex, FliFC interacted with FliGN through extensive hydrophobic contacts similar to those observed in the FliFC-FliGN structure from the thermophile Thermotoga maritima, indicating conservation of the FliFC-FliGN interaction across bacterial species...
December 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29229776/positive-charge-in-the-n-region-of-the-signal-peptide-contributes-to-efficient-post-translational-translocation-of-small-secretory-preproteins
#11
Huan Guo, Jinhong Sun, Xin Li, Yi Xiong, Heting Wang, Hua Shu, Ruimin Zhu, Qi Liu, Yumeng Huang, Rachel Madley, Yulun Wang, Jingqiu Cui, Peter Arvan, Ming Liu
Increasing evidence indicates that many small secretory preproteins can undergo post-translational translocation across the membrane of the endoplasmic reticulum (ER). Although the cellular machinery involved in post-translational translocation of small secretory preproteins has begun to be elucidated, the intrinsic signals contained within these small secretory preproteins that contribute to their efficient post-translational translocation remain unknown. Here, we analyzed the eukaryotic secretory proteome and discovered that it contains an increased percentage of small secretory preproteins with a positive charge in the n-region of the signal peptide (SP)...
December 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29229775/molecular-characterization-of-dxcf-cyanobacteriochromes-from-the-cyanobacterium-acaryochloris-marina-identifies-a-blue-light-power-sensor
#12
Masumi Hasegawa, Keiji Fushimi, Keita Miyake, Takahiro Nakajima, Yuki Oikawa, Gen Enomoto, Moritoshi Sato, Masahiko Ikeuchi, Rei Narikawa
Cyanobacteriochromes (CBCRs) are linear tetrapyrrole-binding photoreceptors that sense a wide range of wavelengths from ultraviolet to far-red. The primary photoreaction in these reactions is a Z/E isomerization of the double bond between rings C and D. After this isomerization, various color-tuning events establish distinct spectral properties of the CBCRs. Among the various CBCRs, the DXCF CBCR lineage is widely distributed among cyanobacteria. Because the DXCF CBCRs from the cyanobacterium Acaryochloris marina vary widely in sequence, we focused on these CBCRs in this study...
December 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29222335/single-cell-transcriptome-sequencing-reveals-that-cell-division-cycle-5-like-protein-is-essential-for-porcine-oocyte-maturation
#13
Xiao-Man Liu, Yan-Kui Wang, Yun-Hua Liu, Xiao-Xia Yu, Pei-Chao Wang, Xuan Li, Zhi-Qiang Du, Cai-Xia Yang
The brilliant cresyl blue (BCB) test is used in both basic biological research and assisted reproduction to identify oocytes likely to be developmentally competent. However, the underlying molecular mechanism targeted by the BCB test is still unclear. To explore this question, we first confirmed that BCB-positive porcine oocytes had higher rates of meiotic maturation, better rates of cleavage and development into blastocysts, and lower death rates. Subsequent single-cell transcriptome sequencing on porcine germinal vesicle (GV)-stage oocytes identified 155 genes that were significantly differentially expressed between BCB-negative and BCB-positive oocytes...
December 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29222334/cellular-flip-long-isoform-cflipl-ikk%C3%AE-interactions-inhibit-irf7-activation-representing-a-new-cellular-strategy-to-inhibit-ifn%C3%AE-expression
#14
Lauren T Gates-Tanzer, Joanna L Shisler
IFNα is important for anti-viral and anticancer defenses. However, over-production is associated with autoimmune disorders. Thus, the cell must precisely up- and down-regulate IFNα to achieve immune system homeostasis. The cellular FLICE-like inhibitory protein (cFLIP) is reported to inhibit IFNα production. However, the mechanism for this antagonism remained unknown. The goal here was to identify this mechanism. Here, we examined the signal transduction events that occur during TLR9- induced IRF7 activation...
December 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29222333/structural-determinants-of-bacterial-lytic-polysaccharide-monooxygenase-functionality
#15
Zarah Forsberg, Bastien Bissaro, Jonathan Gullesen, Bjørn Dalhus, Gustav Vaaje-Kolstad, Vincent G H Eijsink
Bacterial lytic polysaccharide monooxygenases (LPMO10s) use redox chemistry to cleave glycosidic bonds in the two foremost recalcitrant polysaccharides found in nature, namely cellulose and chitin. Analysis of correlated mutations revealed that the substrate-binding and copper-containing surface of LPMO10s comprises a network of coevolved residues and interactions, whose roles in LPMO functionality are unclear. Here, we mutated a subset of these correlated residues in a newly characterized C1/C4-oxidizing LPMO10 from Micromonospora aurantiaca (MaLPMO10B) to the corresponding residues in strictly C1-oxidizing LPMO10s...
December 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29222332/stabilization-of-the-gp120-v3-loop-through-hydrophobic-interactions-reduces-the-immunodominant-v3-directed-non-neutralizing-response-to-hiv-1-envelope-trimers
#16
Steven W de Taeye, Alba Torrents de la Peña, Andrea Vecchione, Enzo Scutigliani, Kwinten Sliepen, Judith A Burger, Patricia van der Woude, Anna Schorcht, Edith E Schermer, Marit J van Gils, Celia C LaBranche, David C Montefiori, Ian A Wilson, John P Moore, Andrew B Ward, Rogier W Sanders
To provide protective immunity against circulating primary HIV-1 strains, a vaccine most likely has to induce broadly neutralizing antibodies (bNAbs) to the HIV-1 envelope (Env) glycoprotein spike. Recombinant Env trimers such as the prototype BG505 SOSIP.664 that closely mimic the native Env spike can induce autologous neutralizing antibodies (NAbs) against relatively resistant (tier-2) primary viruses. Ideally, Env immunogens should present bNAb epitopes, but limit the presentation of immunodominant non-NAb epitopes that might induce off-target and potentially interfering responses...
December 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29222331/a-hypertension-associated-mitochondrial-dna-mutation-introduces-an-m1g37-modification-into-trnamet-altering-its-structure-and-function
#17
Mi Zhou, Ling Xue, Yaru Chen, Haiying Li, Qiufen He, Bibin Wang, Feilong Meng, Meng Wang, Min-Xin Guan
Defective nucleotide modifications of mitochondrial tRNAs have been associated with several human diseases, but their pathophysiology remains poorly understood. In this report, we investigated the pathogenic molecular mechanism underlying a hypertension-associated 4435A>G mutation in mitochondrial tRNAMet The m.4435A>G mutation affected a highly conserved adenosine at position 37, 3' adjacent to the tRNA's anticodon, which is important for the fidelity of codon recognition and stabilization. We hypothesized that the m...
December 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29222330/discovery-of-stimulator-binding-to-a-conserved-pocket-in-the-heme-domain-of-soluble-guanylyl-cyclase
#18
Jessica A Wales, Cheng-Yu Chen, Linda Breci, Andrzej Weichsel, Sylvie G Bernier, James E Sheppeck, Robert Solinga, Takashi Nakai, Paul A Renhowe, Joon Jung, William R Montfort
Soluble guanylyl cyclase (sGC) is the receptor for nitric oxide and a highly sought-after therapeutic target for the management of cardiovascular diseases. New compounds that stimulate sGC show clinical promise, but where these stimulator compounds bind and how they function remains unknown. Here, using a photolyzable diazirine derivative of a novel stimulator compound, IWP-051, and MS analysis, we localized drug binding to the β1 heme domain of sGC proteins from the hawkmoth Manduca sexta and from human. Covalent attachments to the stimulator were also identified in bacterial homologs of the sGC heme domain, referred to as H-NOX domains, including those from Nostoc sp...
December 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29222329/glutaminolysis-is-required-for-tgf-%C3%AE-1-induced-myofibroblast-differentiation-and-activation
#19
Karen Bernard, Naomi J Logsdon, Gloria A Benavides, Yan Sanders, Jianhua Zhang, Victor M Darley-Usmar, Victor J Thannickal
Myofibroblasts participate in physiological wound healing and pathological fibrosis.  Myofibroblast differentiation is characterized by the expression of alpha-smooth muscle actin (α-SMA) and extracellular matrix (ECM) proteins, and is dependent on metabolic reprogramming.  In this study, we explored the role of glutaminolysis and metabolites of the tricarboxylic acid cycle (TCA) in supporting myofibroblast differentiation.  Glutaminolysis converts glutamine (Gln) into alpha-ketoglutarate (α-KG), a critical intermediate in the TCA cycle...
December 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29222328/fructose-and-glucose-regulate-mammalian-target-of-rapamycin-complex-1-and-can-activate-lipogenic-gene-expression-via-distinct-pathways
#20
Yue Hu, Ivana Semova, Xiaowei Sun, Hong Kang, Satyapal Chahar, Anthony N Hollenberg, David Masson, Matthew D Hirschey, Ji Miao, Sudha B Biddinger
Though calorically equivalent to glucose, fructose appears to be more lipogenic, leading to dyslipidemia, fatty liver disease, cardiovascular disease, and diabetes. To better understand how fructose induces lipogenesis, we compared the effects of fructose and glucose on the mTORC1 signaling node, a central regulator of lipogenesis. We found that fructose acutely and transiently suppressed mTORC1 signaling in vitro and in vivo. The constitutive activation of mTORC1 reduced hepatic lipogenic gene expression and produced hypotriglyceridemia after one week of fructose feeding...
December 8, 2017: Journal of Biological Chemistry
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