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https://www.readbyqxmd.com/read/28646141/human-sialidase-neu3-is-s-acylated-and-behaves-like-an-integral-membrane-protein
#1
Macarena Rodriguez-Walker, Jose L Daniotti
Membrane-bound sialidase Neu3 is involved in the catabolism of glycoconjugates, and plays crucial roles in numerous biological processes. Since the mechanism of its association with membranes is still not completely understood, the aim of this work was to provide further information regarding this aspect. Human Neu3 was found to be associated with the plasma membrane and endomembranes, and it was not released from the lipid bilayer under conditions that typically release peripheral membrane proteins. By different experimental approaches, we demonstrated that its C-terminus is exposed to the cytosol while another portion of the protein is exposed to the extracellular space, suggesting that Neu3 possesses the features of a transmembrane protein...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646126/how-a-helix-imposes-palmitoylation-of-a-membrane-protein-what-one-can-learn-from-ncx
#2
Daniel Khananshvili
Palmitoylation is a critical post-translational modification that anchors proteins to, and regulates transport across, the lipid bilayer. Palmitoylation enzymes have been assumed to select their substrates based on a protein's primary sequence, but a consensus sequence has been slow to emerge. A study of the sodium/calcium exchanger now suggests that secondary structure may hold the key to understanding the determinants of this modification.
June 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28645918/phosphorylation-of-argonaute-proteins-affects-mrna-binding-and-is-essential-for-microrna-guided-gene-silencing-in%C3%A2-vivo
#3
Miguel Quévillon Huberdeau, Daniela M Zeitler, Judith Hauptmann, Astrid Bruckmann, Lucile Fressigné, Johannes Danner, Sandra Piquet, Nicholas Strieder, Julia C Engelmann, Guillaume Jannot, Rainer Deutzmann, Martin J Simard, Gunter Meister
Argonaute proteins associate with microRNAs and are key components of gene silencing pathways. With such a pivotal role, these proteins represent ideal targets for regulatory post-translational modifications. Using quantitative mass spectrometry, we find that a C-terminal serine/threonine cluster is phosphorylated at five different residues in human and Caenorhabditis elegans In human, hyper-phosphorylation does not affect microRNA binding, localization, or cleavage activity of Ago2. However, mRNA binding is strongly affected...
June 23, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28645873/generation-of-nitric-oxide-by-olive-olea-europaea-l-pollen-during-in-vitro-germination-and-assessment-of-the-s-nitroso-and-nitro-pollen-proteomes-by-computational-predictive-methods
#4
María José Jimenez-Quesada, Rosario Carmona, Elena Lima-Cabello, José Ángel Traverso, Antonio Jesús Castro, M Gonzalo Claros, Juan de Dios Alché
Nitric oxide is recognized as a signaling molecule involved in a broad range of physiological processes in plants including sexual reproduction. NO has been detected in the pollen grain at high levels and regulates pollen tube growth. Previous studies demonstrated that NO as well as ROS are produced in the olive reproductive tissues in a stage- and tissue-specific manner. The aim of this study was to assess the production of NO throughout the germination of olive (Olea europaea L.) pollen in vitro. The NO fluorescent probe DAF-2DA was used to image NO production in situ, which was correlated to pollen viability...
June 20, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28645654/epigenome-dysregulation-in-cholangiocarcinoma
#5
REVIEW
Colm J O'Rourke, Patricia Munoz-Garrido, Esmeralda L Aguayo, Jesper B Andersen
Epigenomics is a fast-evolving field of research that has lately attracted considerable interest, mainly due to the reversibility of epigenetic marks. Clinically, among solid tumors, the field is still limited. In cholangiocarcinoma (CCA) it is well known that the epigenetic landscape is deregulated both during carcinogenesis and disease progression as a consequence of aberrant mechanisms leading to genome instability. In this article, we will briefly review the molecular alterations that have been described in the transformation of normal cholangiocytes into malignant derivatives, focusing on the role of non-coding RNA (ncRNA) interactions, DNA methylation, post-translational modifications (PTMs) of histones and chromatin remodeling complexes...
June 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28645514/bcl-xl-deamidation-and-cancer-charting-the-fame-trajectories-of-legitimate-child-and-hidden-siblings
#6
REVIEW
Florian Beaumatin, Mohamad El Dhaybi, Claude Bobo, Mireille Verdier, Muriel Priault
Bcl-2 family proteins control programmed cell death through a complex network of interactions within and outside of this family, that are modulated by post-translational modifications (PTM). Bcl-xL, an anti-apoptotic member of this family, is overexpressed in a number of cancers, plays an important role in tumorigenesis and is correlated with drug resistance. Bcl-xL is susceptible to a number of different PTMs. Here, we focus on deamidation. We will first provide an overview of protein deamidation. We will then review how the apoptotic and autophagic functions of Bcl-xL are modified by this PTM, and how this impacts on its oncogenic properties...
June 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28644880/o-glcnacylation-mediates-the-control-of-cytosolic-phosphoenolpyruvate-carboxykinase-activity-via-pgc1%C3%AE
#7
Pedro Latorre, Luis Varona, Carmen Burgos, José A Carrodeguas, Pascual López-Buesa
PGC1α is a coactivator of many transcription factors and cytosolic phosphoenolpyruvate carboxykinase (PCK1) is a key enzyme for gluconeogenesis. PGC1α interacts with the transcription factor PPARγ to stimulate PCK1 expression and thus de novo glucose synthesis. These proteins are not only important for central energy metabolism but also for supplying intermediates for other metabolic pathways, including lipidogenesis and protein synthesis and might therefore be important factors in the ethiopathogenesis of metabolic disorders like diabetes but also in other pathologies like cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28644475/post-translational-modification-of-ribosomally-synthesized-peptides-by-a-radical-sam-epimerase-in-bacillus-subtilis
#8
Alhosna Benjdia, Alain Guillot, Pauline Ruffié, Jérôme Leprince, Olivier Berteau
Ribosomally synthesized peptides are built out of L-amino acids, whereas D-amino acids are generally the hallmark of non-ribosomal synthetic processes. Here we show that the model bacterium Bacillus subtilis is able to produce a novel type of ribosomally synthesized and post-translationally modified peptide that contains D-amino acids, and which we propose to call epipeptides. We demonstrate that a two [4Fe-4S]-cluster radical S-adenosyl-L-methionine (SAM) enzyme converts L-amino acids into their D-counterparts by catalysing Cα-hydrogen-atom abstraction and using a critical cysteine residue as the hydrogen-atom donor...
July 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28644433/ctla-4-mediated-posttranslational-modifications-direct-cytotoxic-t-lymphocyte-differentiation
#9
Holger Lingel, Josef Wissing, Aditya Arra, Denny Schanze, Stefan Lienenklaus, Frank Klawonn, Mandy Pierau, Martin Zenker, Lothar Jänsch, Monika C Brunner-Weinzierl
The blockade of inhibitory receptors such as CTLA-4 (CD152) is being used as immune-checkpoint therapy, offering a powerful strategy to restore effective immune responses against tumors. To determine signal components that are induced under the control of CTLA-4 we analyzed activated murine CD8(+) T cells by quantitative proteomics. Accurate mass spectrometry revealed that CTLA-4 engagement led to central changes in the phosphorylation of proteins involved in T-cell differentiation. Beside other targets, we discovered a CTLA-4-mediated induction of the translational inhibitor programmed cell death-4 (PDCD4) as a result of FoxO1 nuclear re-localization...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644070/particulate-matter-disrupts-human-lung-endothelial-cell-barrier-integrity-via-rho-dependent-pathways
#10
Ting Wang, Yuka Shimizu, Xiaomin Wu, Gabriel T Kelly, Xiaoyan Xu, Lichun Wang, Zhongqing Qian, Yin Chen, Joe G N Garcia
Increased exposure to ambient particulate matter (PM) is associated with elevated morbidity and mortality in patients with cardiopulmonary diseases and cancer. We and others have shown that PM induces lung microvascular barrier dysfunction which potentially enhances the systemic toxicity of PM. However, the mechanisms by which PM disrupts vascular endothelial integrity remain incompletely explored. We hypothesize that PM induces endothelial cell (EC) cytoskeleton rearrangement via Rho GTPase-dependent pathways to facilitate vascular hyperpermeability...
June 23, 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28644004/the-intricate-effects-of-alpha-amino-and-lysine-modifications-on-arginine-methylation-on-the-n-terminal-tail-of-histone-h4
#11
Melody D Fulton, Jing Zhang, Maomao He, Meng-Chiao Ho, Y George Zheng
Chemical modifications on the DNA and nucleosomal histones tightly control the gene transcription program in eukaryotic cells. The "histone code" hypothesis proposes that the frequency, combination, and location of post-translational modifications (PTMs) on the core histones compose a complex network of epigenetic regulation. Currently, there are at least 23 different types and over 450 histone PTMs discovered, and the PTMs on lysine and arginine residues account for a crucial part of the histone code. Although significant progress has been achieved in recent years, the molecular basis for the histone code is far from being fully understood...
June 23, 2017: Biochemistry
https://www.readbyqxmd.com/read/28643003/recent-developments-in-solution-nuclear-magnetic-resonance-nmr-based-molecular-biology
#12
REVIEW
Joshua J Ziarek, Diego Baptista, Gerhard Wagner
Visualizing post-translational modifications, conformations, and interaction surfaces of protein structures at atomic resolution underpins the development of novel therapeutics to combat disease. As computational resources expand, in silico calculations coupled with experimentally derived structures and functional assays have led to an explosion in structure-based drug design (SBDD) with several compounds in clinical trials. It is increasingly clear that "hidden" transition-state structures along activation trajectories can be harnessed to develop novel classes of allosteric inhibitors...
June 23, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28639249/histone-post-translational-modifications-and-nucleosome-organisation-in-transcriptional-regulation-some-open-questions
#13
Josefa Castillo, Gerardo López-Rodas, Luis Franco
The organisation of chromatin is first discussed to conclude that nucleosomes play both structural and transcription-regulatory roles. The presence of nucleosomes makes difficult the access of transcriptional factors to their target sequences and the action of RNA polymerases. The histone post-translational modifications and nucleosome remodelling are first discussed, from a historical point of view, as mechanisms to remove the obstacles imposed by chromatin structure to transcription. Instead of reviewing the state of the art of the whole field, this review is centred on some open questions...
June 22, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28638922/-palmitoylation-of-heat-shock-protein-90-in-mouse-sperm
#14
Rui Li, Kun Li, Yue Yang, Pei-Bei Sun, Ai-Jun Chen, Ya Ni
Protein palmitoylation, one of post-translation modifications, refers to the addition of saturated 16-carbon palmitic acid to cysteine residues via the thioester bond. It plays key roles in various functional activities, such as the interaction, stability and location of proteins. Heat shock protein 90 (Hsp90), an important molecular chaperone, has been reported to be involved in sperm capacitation. However, it remains unclear whether protein palmitoylation exists in sperm and whether Hsp90 in sperm is palmitoylated under different physiological conditions...
June 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28637931/comparative-miromics-of-salt-tolerant-and-salt-sensitive-rice
#15
Kavita Goswami, Anita Tripathi, Neeti Sanan-Mishra
Increase in soil salt causes osmotic and ionic stress to plants, which inhibits their growth and productivity. Rice production is also hampered by salinity and the effect of salt is most severe at the seedling and reproductive stages. Salainity tolerance is a quantitative property controlled by multiple genes coding for signaling molecules, ion transporters, metabolic enzymes and transcription regulators. MicroRNAs are key modulators of gene-expression that act at the post-transcriptional level by translation repression or transcript cleavage...
June 22, 2017: Journal of Integrative Bioinformatics
https://www.readbyqxmd.com/read/28636386/msviz-a-graphical-software-tool-for-in-depth-manual-validation-and-quantitation-of-post-translational-modifications
#16
Trinidad Martin Campos, Roman Mylonas, Alexandre Masselot, Patrice Waridel, Tanja Petricevic, Ioannis Xenarios, Manfredo Quadroni
Mass spectrometry (MS) has become the tool of choice for the large scale identification and quantitation of proteins and their post-translational modifications (PTMs). This development has been enabled by powerful software packages for the automated analysis of MS data. While data on PTM's of thousands of proteins can nowadays be readily obtained, fully deciphering the complexity and combinatorics of modification patterns even on a single protein often remains challenging. Moreover, functional investigation of PTMs on a protein of interest requires validation of the localization and the accurate quantitation of its changes across several conditions, tasks that often still require human evaluation...
June 21, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28636189/discovery-of-alkyl-bis-oxy-dibenzimidamide-derivatives-as-novel-protein-arginine-methyltransferase-1-prmt1-inhibitors
#17
Wei-Yao Zhang, Wen-Chao Lu, Hao Jiang, Zheng-Bing Lv, Yi-Qian Xie, Fu-Lin Lian, Zhong-Jie Liang, Yu-Xi Jiang, Da-Jin Wang, Cheng Luo, Jia Jin, Fei Ye
Protein arginine methylation, a post-translational modification critical for a variety of biological processes, is catalyzed by protein arginine N-methyltransferases (PRMTs). In particular, PRMT1 is responsible for over 85% of the arginine methylation in mammalian cells. Dysregulation of PRMT1 is involved in diverse pathological diseases including cancers. However, most current PRMT1inhibitors are lack of specificity, efficacy, and bioavailability. Herein, a series of alkyl bis(oxy)dibenzimidamide derivatives were identified as selective PRMT1 inhibitors...
June 21, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28634440/cysteines-as-redox-molecular-switches-and-targets-of-disease
#18
REVIEW
Annamaria Fra, Edgar D Yoboue, Roberto Sitia
Thiol groups can undergo numerous modifications, making cysteine a unique molecular switch. Cysteine plays structural and regulatory roles as part of proteins or glutathione, contributing to maintain redox homeostasis and regulate signaling within and amongst cells. Not surprisingly therefore, cysteines are associated with many hereditary and acquired diseases. Mutations in the primary protein sequence (gain or loss of a cysteine) are most frequent in membrane and secretory proteins, correlating with the key roles of disulfide bonds...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28632996/taking-control-hijacking-of-rab-gtpases-by-intracellular-bacterial-pathogens
#19
Stefania Spanò, Jorge E Galán
Intracellular bacterial pathogens survive and replicate within specialized eukaryotic cell organelles. To establish their intracellular niches these pathogens have adopted sophisticated strategies to control intracellular membrane trafficking. Since Rab-family GTPases are critical regulators of endocytic and secretory membrane trafficking events, many intracellular pathogens have evolved specific mechanisms to modulate or hijack Rab GTPases dynamics and trafficking functions. One such strategy is the delivery of bacterial effectors through specialized machines to specifically target Rab GTPases...
June 20, 2017: Small GTPases
https://www.readbyqxmd.com/read/28631261/distinct-post-translational-features-of-type-i-collagen-are-conserved-in-mouse-and-human-periodontal-ligament
#20
D M Hudson, M Garibov, D R Dixon, T Popowics, D R Eyre
BACKGROUND AND OBJECTIVE: Specifics of the biochemical pathways that modulate collagen cross-links in the periodontal ligament (PDL) are not fully defined. Better knowledge of the collagen post-translational modifications that give PDL its distinct tissue properties is needed to understand the pathogenic mechanisms of human PDL destruction in periodontal disease. In this study, the post-translational phenotypes of human and mouse PDL type I collagen were surveyed using mass spectrometry...
June 20, 2017: Journal of Periodontal Research
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