scholarly journals Sirtuin-dependent reversible lysine acetylation of glutamine synthetases reveals an autofeedback loop in nitrogen metabolism

2016 ◽  
Vol 113 (24) ◽  
pp. 6653-6658 ◽  
Author(s):  
Di You ◽  
Bin-Cheng Yin ◽  
Zhi-Hai Li ◽  
Ying Zhou ◽  
Wen-Bang Yu ◽  
...  
Keyword(s):  
Nitrogen Metabolism ◽  
Feedback Regulation ◽  
Nutrient Sensing ◽  
Saccharopolyspora Erythraea ◽  
Regulatory Function ◽  
Lysine Acetylation ◽  
Cellular Processes ◽  
Domains Of Life ◽  
Lysine Acetyltransferase ◽  
Response To Environmental Change

In cells of all domains of life, reversible lysine acetylation modulates the function of proteins involved in central cellular processes such as metabolism. In this study, we demonstrate that the nitrogen regulator GlnR of the actinomycete Saccharopolyspora erythraea directly regulates transcription of the acuA gene (SACE_5148), which encodes a Gcn5-type lysine acetyltransferase. We found that AcuA acetylates two glutamine synthetases (GlnA1 and GlnA4) and that this lysine acetylation inactivated GlnA4 (GSII) but had no significant effect on GlnA1 (GSI-β) activity under the conditions tested. Instead, acetylation of GlnA1 led to a gain-of-function that modulated its interaction with the GlnR regulator and enhanced GlnR–DNA binding. It was observed that this regulatory function of acetylated GSI-β enzymes is highly conserved across actinomycetes. In turn, GlnR controls the catalytic and regulatory activities (intracellular acetylation levels) of glutamine synthetases at the transcriptional and posttranslational levels, indicating an autofeedback loop that regulates nitrogen metabolism in response to environmental change. Thus, this GlnR-mediated acetylation pathway provides a signaling cascade that acts from nutrient sensing to acetylation of proteins to feedback regulation. This work presents significant new insights at the molecular level into the mechanisms underlying the regulation of protein acetylation and nitrogen metabolism in actinomycetes.

SUBSTANTIATION OF NECESSITY OF APPLICATION OF PHOSPHOLIPIDS IN THE PRODUCTION OF FUNCTIONAL FOODSTUFFS

2018 ◽  
Author(s):  
Н.Н. КОРНЕН ◽  
С.А. КАЛМАНОВИЧ ◽  
Т.А. ШАХРАЙ ◽  
Е.П. ВИКТОРОВА
Keyword(s):  
Nutritional Status ◽  
Dietary Supplements ◽  
Physiological Role ◽  
Regulatory Function ◽  
Medical Sciences ◽  
Cellular Processes ◽  
Level Of Knowledge ◽  
Protective Fabrics ◽  
Technological University

Проведен анализ современных научных представлений о роли фосфолипидов (ФЛ) в обеспечении функционирования биомембран и их регуляторной функции в важнейших клеточных процессах. Из ФЛ состоит 50% печени, 1/3 мозговых изолирующих и защитных тканей, окружающих головной и спинной мозг. По рекомендациям РАМН, физиологическая потребность взрослого человека в ФЛ составляет 5–7 г/сут. Согласно проведенным исследованиям, в пищевом статусе населения РФ дефицит ФЛ составляет от 50 до 80%. Показано, что современный уровень знаний о физиологической роли ФЛ способствует созданию и внедрению в производство фосфолипидных продуктов на основе ФЛ и фосфолипидных БАД на основе растительных лецитинов, употребление которых может нормализовать пищевой статус. Дано описание фосфолипидных продуктов и БАД серии Тонус (Супер-Тонус, Фито-Тонус, Тонус-Плюс) и серии Витол (Витол, Витол-Холин и Витол-ФЭИ), разработанных учеными Кубанского государственного технологического университета. Показаны возможности применения растительных лецитинов, фосфолипидных продуктов и БАД на их основе в качестве многофункциональных рецептурных компонентов при производстве пищевых продуктов функционального и специализированного назначения. The analysis of modern scientific ideas about the role of phospholipids (FL) in ensuring the functioning of biomembranes and their regulatory function in the most important cellular processes is carried out. So, 50% of a liver, 1/3 brain isolating and protective fabrics surrounding a brain and spinal cord consist of FL. According to the recommendations of the Russian Academy of Medical Sciences, the physiological need of an adult in FL is 5–7 g/day. According to the conducted studies, in the nutritional status of the Russian population, the deficit of FL is from 50 to 80%. It is shown that the current level of knowledge about the physiological role of FL contributes to the creation and introduction of phospholipid products based on FL and phospholipid supplements on the basis of vegetable lecithins, the use of which can normalize the nutritional status. The description of phospholipid products and dietary supplements developed by scientists of the Kuban State Technological University of the Tonus series (Super Tonus, Phyto Tonus, Tonus Plus) and the Vitol series (Vitol, Vitol Kholin and Vitol FEI) is given. The possibilities of using vegetable lecithins, phospholipid products and dietary supplements on their basis are shown as multifunctional prescription components in the production of functional and specialized food products.

GlnR-mediated regulation of nitrogen metabolism in the actinomycete Saccharopolyspora erythraea

2014 ◽  
Vol 98 (18) ◽  
pp. 7935-7948 ◽  
Author(s):  
Li-Li Yao ◽  
Cheng-Heng Liao ◽  
Gang Huang ◽  
Ying Zhou ◽  
Sebastien Rigali ◽  
...  
Keyword(s):  
Nitrogen Metabolism ◽  
Saccharopolyspora Erythraea

Deep learning based prediction of reversible HAT/HDAC-specific lysine acetylation

2019 ◽  
Vol 21 (5) ◽  
pp. 1798-1805 ◽  
Author(s):  
Kai Yu ◽  
Qingfeng Zhang ◽  
Zekun Liu ◽  
Yimeng Du ◽  
Xinjiao Gao ◽  
...  
Keyword(s):  
Deep Learning ◽  
Protein Interactions ◽  
Web Server ◽  
Data Sets ◽  
Lysine Acetylation ◽  
Protein Acetylation ◽  
Protein Protein Interactions ◽  
Cellular Processes ◽  
Protein Lysine Acetylation ◽  
Specific Regulation

Abstract Protein lysine acetylation regulation is an important molecular mechanism for regulating cellular processes and plays critical physiological and pathological roles in cancers and diseases. Although massive acetylation sites have been identified through experimental identification and high-throughput proteomics techniques, their enzyme-specific regulation remains largely unknown. Here, we developed the deep learning-based protein lysine acetylation modification prediction (Deep-PLA) software for histone acetyltransferase (HAT)/histone deacetylase (HDAC)-specific acetylation prediction based on deep learning. Experimentally identified substrates and sites of several HATs and HDACs were curated from the literature to generate enzyme-specific data sets. We integrated various protein sequence features with deep neural network and optimized the hyperparameters with particle swarm optimization, which achieved satisfactory performance. Through comparisons based on cross-validations and testing data sets, the model outperformed previous studies. Meanwhile, we found that protein–protein interactions could enrich enzyme-specific acetylation regulatory relations and visualized this information in the Deep-PLA web server. Furthermore, a cross-cancer analysis of acetylation-associated mutations revealed that acetylation regulation was intensively disrupted by mutations in cancers and heavily implicated in the regulation of cancer signaling. These prediction and analysis results might provide helpful information to reveal the regulatory mechanism of protein acetylation in various biological processes to promote the research on prognosis and treatment of cancers. Therefore, the Deep-PLA predictor and protein acetylation interaction networks could provide helpful information for studying the regulation of protein acetylation. The web server of Deep-PLA could be accessed at http://deeppla.cancerbio.info.

scholarly journals A Mep2-dependent Transcriptional Profile Links Permease Function to Gene Expression during Pseudohyphal Growth in Saccharomyces cerevisiae

2008 ◽  
Vol 19 (7) ◽  
pp. 3028-3039 ◽  
Author(s):  
Julian C. Rutherford ◽  
Gordon Chua ◽  
Timothy Hughes ◽  
Maria E. Cardenas ◽  
Joseph Heitman
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Map Kinase ◽  
Molecular Mechanisms ◽  
Nutrient Sensing ◽  
Transcriptional Profile ◽  
Regulatory Function ◽  
Pseudohyphal Growth ◽  
Epistasis Analysis ◽  
Map Kinase Pathway ◽  
Kinase Pathway

The ammonium permease Mep2 is required for the induction of pseudohyphal growth, a process in Saccharomyces cerevisiae that occurs in response to nutrient limitation. Mep2 has both a transport and a regulatory function, supporting models in which Mep2 acts as a sensor of ammonium availability. Potentially similar ammonium permease-dependent regulatory cascades operate in other fungi, and they may also function in animals via the homologous Rh proteins; however, little is known about the molecular mechanisms that mediate ammonium sensing. We show that Mep2 is localized to the cell surface during pseudohyphal growth, and it is required for both filamentous and invasive growth. Analysis of site-directed Mep2 mutants in residues lining the ammonia-conducting channel reveal separation of function alleles (transport and signaling defective; transport-proficient/signaling defective), indicating transport is necessary but not sufficient to sense ammonia. Furthermore, Mep2 overexpression enhances differentiation under normally repressive conditions and induces a transcriptional profile that is consistent with activation of the mitogen-activated protein (MAP) kinase pathway. This finding is supported by epistasis analysis establishing that the known role of the MAP kinase pathway in pseudohyphal growth is linked to Mep2 function. Together, these data strengthen the model that Mep2-like proteins are nutrient sensing transceptors that govern cellular differentiation.

scholarly journals Lysine Acetylation Regulates Alanyl-tRNA Synthetase Activity in Escherichia coli

Genes ◽  
2018 ◽  
Vol 9 (10) ◽  
pp. 473 ◽  
Author(s):  
Takuya Umehara ◽  
Saori Kosono ◽  
Dieter Söll ◽  
Koji Tamura
Keyword(s):  
Escherichia Coli ◽  
Trna Synthetase ◽  
Synthetase Activity ◽  
Lysine Acetylation ◽  
Trna Synthetases ◽  
E Coli ◽  
Domains Of Life ◽  
The Impact

Protein lysine acetylation is a widely conserved posttranslational modification in all three domains of life. Lysine acetylation frequently occurs in aminoacyl-tRNA synthetases (aaRSs) from many organisms. In this study, we determined the impact of the naturally occurring acetylation at lysine-73 (K73) in Escherichia coli class II alanyl-tRNA synthetase (AlaRS) on its alanylation activity. We prepared an AlaRS K73Ac variant in which Nε-acetyl-l-lysine was incorporated at position 73 using an expanded genetic code system in E. coli. The AlaRS K73Ac variant showed low activity compared to the AlaRS wild type (WT). Nicotinamide treatment or CobB-deletion in an E. coli led to elevated acetylation levels of AlaRS K73Ac and strongly reduced alanylation activities. We assumed that alanylation by AlaRS is affected by K73 acetylation, and the modification is sensitive to CobB deacetylase in vivo. We also showed that E. coli expresses two CobB isoforms (CobB-L and CobB-S) in vivo. CobB-S displayed the deacetylase activity of the AlaRS K73Ac variant in vitro. Our results imply a potential regulatory role for lysine acetylation in controlling the activity of aaRSs and protein synthesis.

scholarly journals Bioinformatics of Metalloproteins and Metalloproteomes

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3366
Author(s):  
Yan Zhang ◽  
Junge Zheng
Keyword(s):  
Comparative Genomics ◽  
Metal Binding ◽  
Computational Prediction ◽  
Bioinformatic Analysis ◽  
Research Progress ◽  
Evolutionary Patterns ◽  
Cellular Processes ◽  
Metal Binding Sites ◽  
Domains Of Life ◽  
Systematic Understanding

Trace metals are inorganic elements that are required for all organisms in very low quantities. They serve as cofactors and activators of metalloproteins involved in a variety of key cellular processes. While substantial effort has been made in experimental characterization of metalloproteins and their functions, the application of bioinformatics in the research of metalloproteins and metalloproteomes is still limited. In the last few years, computational prediction and comparative genomics of metalloprotein genes have arisen, which provide significant insights into their distribution, function, and evolution in nature. This review aims to offer an overview of recent advances in bioinformatic analysis of metalloproteins, mainly focusing on metalloprotein prediction and the use of different metals across the tree of life. We describe current computational approaches for the identification of metalloprotein genes and metal-binding sites/patterns in proteins, and then introduce a set of related databases. Furthermore, we discuss the latest research progress in comparative genomics of several important metals in both prokaryotes and eukaryotes, which demonstrates divergent and dynamic evolutionary patterns of different metalloprotein families and metalloproteomes. Overall, bioinformatic studies of metalloproteins provide a foundation for systematic understanding of trace metal utilization in all three domains of life.

scholarly journals Identification of anN-Acetylglucosamine Transporter That Mediates Hyphal Induction inCandida albicans

2007 ◽  
Vol 18 (3) ◽  
pp. 965-975 ◽  
Author(s):  
Francisco J. Alvarez ◽  
James B. Konopka
Keyword(s):  
Plasma Membrane ◽  
Hyphal Growth ◽  
Nutrient Sensing ◽  
Major Facilitator Superfamily ◽  
Cellular Processes ◽  
Macrophage Phagocytosis ◽  
Wide Range ◽  
High Concentrations ◽  
Hyphal Formation ◽  
Major Facilitator

The sugar N-acetylglucosamine (GlcNAc) plays an important role in nutrient sensing and cellular regulation in a wide range of organisms from bacteria to humans. In the fungal pathogen Candida albicans, GlcNAc induces a morphological transition from budding to hyphal growth. Proteomic comparison of plasma membrane proteins from buds and from hyphae induced by GlcNAc identified a novel hyphal protein (Ngt1) with similarity to the major facilitator superfamily of transporters. An Ngt1-GFP fusion was detected in the plasma membrane after induction with GlcNAc, but not other related sugars. Ngt1-GFP was also induced by macrophage phagocytosis, suggesting a role for the GlcNAc response in signaling entry into phagolysosomes. NGT1 is needed for efficient GlcNAc uptake and for the ability to induce hyphae at low GlcNAc concentrations. High concentrations of GlcNAc could bypass the need for NGT1 to induce hyphae, indicating that elevated intracellular levels of GlcNAc induce hyphal formation. Expression of NGT1 in Saccharomyces cerevisiae promoted GlcNAc uptake, indicating that Ngt1 acts directly as a GlcNAc transporter. Transport mediated by Ngt1 was specific, as other sugars could not compete for the uptake of GlcNAc. Thus, Ngt1 represents the first eukaryotic GlcNAc transporter to be discovered. The presence of NGT1 homologues in the genome sequences of a wide range of eukaryotes from yeast to mammals suggests that they may also function in the cellular processes regulated by GlcNAc, including those that underlie important diseases such as cancer and diabetes.

scholarly journals Mechanisms of cross-talk between G-protein-coupled receptors resulting in enhanced release of intracellular Ca2+

2003 ◽  
Vol 374 (2) ◽  
pp. 281-296 ◽  
Author(s):  
Tim D. WERRY ◽  
Graeme F. WILKINSON ◽  
Gary B. WILLARS
Keyword(s):  
G Protein ◽  
Cross Talk ◽  
Cell Function ◽  
Feedback Regulation ◽  
G Protein Coupled Receptors ◽  
Negative Feedback Regulation ◽  
Cellular Processes ◽  
Heterologous Desensitization ◽  
G Protein Coupled

Alteration in [Ca2+]i (the intracellular concentration of Ca2+) is a key regulator of many cellular processes. To allow precise regulation of [Ca2+]i and a diversity of signalling by this ion, cells possess many mechanisms by which they are able to control [Ca2+]i both globally and at the subcellular level. Among these are many members of the superfamily of GPCRs (G-protein-coupled receptors), which are characterized by the presence of seven transmembrane domains. Typically, those receptors able to activate PLC (phospholipase C) enzymes cause release of Ca2+ from intracellular stores and influence Ca2+ entry across the plasma membrane. It has been well documented that Ca2+ signalling by one type of GPCR can be influenced by stimulation of a different type of GPCR. Indeed, many studies have demonstrated heterologous desensitization between two different PLC-coupled GPCRs. This is not surprising, given our current understanding of negative-feedback regulation and the likely shared components of the signalling pathway. However, there are also many documented examples of interactions between GPCRs, often coupling preferentially to different signalling pathways, which result in a potentiation of Ca2+ signalling. Such interactions have important implications for both the control of cell function and the interpretation of in vitro cell-based assays. However, there is currently no single mechanism that adequately accounts for all examples of this type of cross-talk. Indeed, many studies either have not addressed this issue or have been unable to determine the mechanism(s) involved. This review seeks to explore a range of possible mechanisms to convey their potential diversity and to provide a basis for further experimental investigation.

scholarly journals Specific and Covalent Targeting of Conjugating and Deconjugating Enzymes of Ubiquitin-Like Proteins

2004 ◽  
Vol 24 (1) ◽  
pp. 84-95 ◽  
Author(s):  
Joris Hemelaar ◽  
Anna Borodovsky ◽  
Benedikt M. Kessler ◽  
David Reverter ◽  
Julie Cook ◽  
...  
Keyword(s):  
Protein Modification ◽  
Cell Cycle Progression ◽  
Expression Profiles ◽  
Mouse Cell ◽  
Regulatory Function ◽  
Tissue Specific ◽  
Active Site Cysteine ◽  
Cellular Processes ◽  
Specific Protease ◽  
Enzymatic Pathways

ABSTRACT Modification of proteins by ubiquitin (Ub)-like proteins (UBLs) plays an important role in many cellular processes, including cell cycle progression, nuclear transport, and autophagy. Protein modification occurs via UBL-conjugating and -deconjugating enzymes, which presumably exert a regulatory function by determining the conjugation status of the substrate proteins. To target and identify UBL-modifying enzymes, we produced Nedd8, ISG15, and SUMO-1 in Escherichia coli and equipped them with a C-terminal electrophilic trap (vinyl sulfone [VS]) via an intein-based method. These C-terminally modified UBL probes reacted with purified UBL-activating (E1), -conjugating (E2), and -deconjugating enzymes in a covalent fashion. Modified UBLs were radioiodinated and incubated with cell lysates prepared from mouse cell lines and tissues to allow visualization of polypeptides reactive with individual UBL probes. The cell type- and tissue-specific labeling patterns observed for the UBL probes reflect distinct expression profiles of active enzymes, indicating tissue-specific functions of UBLs. We identify Ub C-terminal hydrolase L1 (UCH-L1) and DEN1/NEDP1/SENP8, in addition to UCH-L3, as proteases with specificity for Nedd8. The Ub-specific protease isopeptidase T/USP5 is shown to react with ISG15-VS. Furthermore, we demonstrate that the desumoylation enzyme SuPr-1 can be modified by SUMO-1-VS, a modification that is dependent on the SuPr-1 active-site cysteine. The UBL probes described here will be valuable tools for the further characterization of the enzymatic pathways that govern modification by UBLs.

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