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FEBS Journal

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https://www.readbyqxmd.com/read/28516732/diadenosine-tetraphosphate-ap4a-an-e-coli-alarmone-or-a-damage-metabolite
#1
Dragana Despotović, Alexander Brandis, Alon Savidor, Yishai Levin, Laura Fumagalli, Dan S Tawfik
Under stress, metabolism is changing: specific up- or down-regulation of proteins and metabolites occurs as well as side-effects. Distinguishing specific stress-signaling metabolites (alarmones) from side-products (damage metabolites) is not trivial. One example is diadenosine tetraphosphate, Ap4A - a side-product of aminoacyl-tRNA synthetases found in all domains of life. The earliest observations suggested that Ap4A serves as an alarmone for heat stress in E. coli. However, despite 50 years of research, the signaling mechanisms associated with Ap4A remain unknown...
May 18, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28504865/real-time-crystallographic-studies-of-the-adenine-riboswitch-using-an-x-ray-free-electron-laser
#2
REVIEW
J R Stagno, Y R Bhandari, C E Conrad, Y Liu, Y-X Wang
Structures of the four reaction states of the adenine riboswitch aptamer domain, including a transient intermediate state were solved by serial femtosecond crystallography. The structures not only demonstrate the use of X-ray free electron lasers for RNA crystallography but have also proven that transient states can be determined in real time by mix-and-inject crystallography. These results illustrate the structural basis for the ligand-induced conformational changes associated with the molecular "switch". This article is protected by copyright...
May 15, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28504839/the-pathological-trento-variant-of-alpha-1-antitrypsin-e75v-shows-non-classical-behaviour-during-polymerization
#3
Elena Miranda, Ilaria Ferrarotti, Romina Berardelli, Mattia Laffranchi, Marta Cerea, Fabrizio Gangemi, Imran Haq, Stefania Ottaviani, David A Lomas, James A Irving, Annamaria Fra
Severe alpha-1-antitrypsin deficiency (AATD) is most frequently associated with the alpha-1-antitrypsin (AAT) Z variant (E342K). ZZ homozygotes exhibit accumulation of AAT as polymers in the endoplasmic reticulum of hepatocytes. This protein deposition can lead to liver disease, with the resulting low circulating levels of AAT predisposing to early-onset emphysema due to dysregulation of elastinolytic activity in the lungs. An increasing number of rare AAT alleles have been identified in patients with severe AATD, typically in combination with the Z allele...
May 15, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28500793/integrating-the-genomic-architecture-of-human-nucleolar-organizer-regions-with-the-biophysical-properties-of-nucleoli
#4
REVIEW
Hazel Mangan, Michael Ó Gailín, Brian McStay
Nucleoli are the sites of ribosome biogenesis and the largest membraneless sub-nuclear structures. They are intimately linked with growth and proliferation control and function as sensors of cellular stress. Nucleoli form around arrays of ribosomal gene (rDNA) repeats also called nucleolar organizer regions (NORs). In humans, NORs are located on the short arms of all five human acrocentric chromosomes. Multiple NORs contribute to the formation of large heterochromatin-surrounded nucleoli observed in most human cells...
May 13, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28500788/unraveling-the-importance-of-the-malaria-parasite-helicases
#5
REVIEW
Renu Tuteja
Malaria is a human parasitic disease caused by infection from Plasmodium species, particularly Plasmodium falciparum. Each year millions of people are infected with malaria and large numbers of deaths result due to this deadly infection. P. falciparum contains 14 chromosomes, nearly 5400 genes and a multistage life cycle in humans and mosquitoes. The control of malaria is still a challenge as the parasite is continuously developing resistance to available anti-malarial drugs and the mosquito vector is developing resistance to insecticides...
May 13, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28500775/vaccines-against-malaria-still-a-long-way-to-go
#6
REVIEW
Kai Matuschewski
Several species of Plasmodium cause a broad spectrum of human disease that range from nausea and fever to severe anemia, cerebral malaria, and multi-organ failure. In malaria-endemic countries continuous exposure to Plasmodium sporozoite inoculations and subsequent blood infections elicit only partial and short-lived immunity, which gradually develops over many years of parasite exposure and multiple clinical episodes. The ambitious goal of malaria vaccinology over the past 70 years has been to develop an immunization strategy that mounts protection superior to naturally acquired immunity...
May 13, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28500773/the-energy-sensing-lkb1-ampk%C3%AE-1-pathway-regulates-igf1-secretion-and-consequent-activation-of-the-igf1r-pkb-pathway-in-primary-hepatocytes
#7
Liang Chen, Qiaoli Chen, Ping Rong, Hong Yu Wang, Shuai Chen
The insulin-like growth factor 1 (IGF1) pathway has been linked with various diseases including diabetes, cancer and aging. In contrast to the well-established regulatory mechanisms controlling IGF1 expression, molecular mechanisms regulating of its secretion is not fully understood. The AMP-activated protein kinase (AMPK) is a key energy sensor, and accumulative evidence shows that AMPK is an attractive therapeutic target for treatment of diabetes, cancer and aging. Here we found that deficiency of AMPK promoted IGF1 secretion in mouse primary hepatocytes...
May 13, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28497654/oxidative-stickland-reactions-in-an-obligate-aerobic-organism-amino-acid-catabolism-in-the-crenarchaeon-sulfolobus-solfataricus
#8
Helge Stark, Jacqueline Wolf, Andreas Albersmeier, Trong K Pham, Julia D Hofmann, Bettina Siebers, Jörn Kalinowski, Phillip C Wright, Meina Neumann-Schaal, Dietmar Schomburg
The thermoacidophilic Crenarchaeon Sulfolobus solfataricus is a model organism for archaeal adaptation to extreme environments and renowned for its ability to degrade a broad variety of substrates. It has been well characterised concerning the utilisation of numerous carbohydrates as carbon source. However, its amino acid metabolism, especially the degradation of single amino acids, is not as well understood. In this work, we performed metabolic modelling as well as metabolome, transcriptome and proteome analysis on cells grown on caseinhydrolysate as carbon source in order to draw a comprehensive picture of amino acid metabolism in S...
May 12, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28488757/stimulation-of-pol-iii-dependent-5s-rrna-and-u6-snrna-gene-expression-by-ap-1-transcription-factors
#9
Richa Ahuja, Vijay Kumar
RNA polymerase III transcribes structurally diverse group of essential non-coding RNAs including 5S rRNA and U6 snRNA. These non-coding RNAs are involved in RNA processing and ribosome biogenesis, thus, coupling Pol III activity to the rate of protein synthesis, cell growth and proliferation. Even though a few Pol II-associated transcription factors have been reported to participate in Pol III-dependent transcription, its activation by AP-1 factors c-Fos and c-Jun has remained unexplored. Here, we show that c-Fos and c-Jun bind to specific sites in the regulatory regions of 5S rRNA (type I) and U6 snRNA (type III) gene promoters and stimulate their transcription...
May 10, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28485897/three-dimensional-structures-and-functional-studies-of-two-gh43-arabinofuranosidases-from-weissella-sp-strain-142-and-lactobacillus-brevis
#10
Javier A Linares-Pastén, Peter Falck, Khalil Albasri, Sven Kjellström, Patrick Adlercreutz, Derek T Logan, Eva Nordberg Karlsson
Arabinofuranosidases degrade arabinose-containing oligo and polysaccharides, releasing L-arabinose, which is a potentially useful sugar, shown to reduce glycemic response under certain conditions. Arabinofuranosidases (Arafs) are frequently found in GH43, one of the most common GH-families encoded in genomes in gut microbiota, and hence it is of interest to increase understanding of the function of these enzymes in species occurring in the gut. Here we have produced, characterized and solved the three-dimensional structures, at 1...
May 9, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28485891/%C3%AE-syntrophin-stabilises-catalase-to-reduce-endogenous-reactive-oxygen-species-levels-during-myoblast-differentiation
#11
Jae Yun Moon, Su Jin Choi, Cheol Ho Heo, Hwan Myung Kim, Hye Sun Kim
α-Syntrophin is a component of the dystrophin-glycoprotein complex that interacts with various intracellular signaling proteins in muscle cells. The α-syntrophin knock-down C2 cell line (SNKD), established by infecting lentivirus particles with α-syntrophin shRNA, is characterized by a defect in terminal differentiation and increase in cell death. Since myoblast differentiation is accompanied by intensive mitochondrial biogenesis, the generation of intracellular reactive oxygen species (ROS) is also increased during myogenesis...
May 9, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28485854/podocyte-specific-soluble-epoxide-hydrolase-deficiency-in-mice-attenuates-acute-kidney-injury
#12
Ahmed Bettaieb, Shinichiro Koike, Samah Chahed, Yi Zhao, Santana Bachaalany, Nader Hashoush, James Graham, Fatima Huma, Peter J Havel, Artiom Gruzdev, Darryl C Zeldin, Bruce D Hammock, Fawaz G Haj
Podocytes play an important role in maintaining glomerular function, and podocyte injury is a significant component in the pathogenesis of proteinuria. Soluble epoxide hydrolase (sEH) is a cytosolic enzyme whose genetic deficiency and pharmacological inhibition have beneficial effects on renal function, but its role in podocytes remains unexplored. The objective of this study was to investigate the contribution of sEH in podocytes to lipopolysaccharide (LPS)-induced kidney injury. We report increased sEH transcript and protein expression in murine podocytes upon LPS challenge...
May 9, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28485824/crystal-structure-of-plant-acetohydroxyacid-synthase-the-target-for-several-commercial-herbicides
#13
Mario Daniel Garcia, Jian-Guo Wang, Thierry Lonhienne, Luke William Guddat
Acetohydroxyacid synthase (AHAS, E.C. 2.2.1.6) is the first enzyme in the branched-chain amino acid biosynthesis pathway. Five of the most widely used commercial herbicides (i.e. sulfonylureas, imidazolinones, triazolopyrimidines, pyrimidinyl-benzoates and sulfonylamino-cabonyl-triazolinones) target this enzyme. Here we have determined the first crystal structure of a plantAHAS in the absence of any inhibitor (2.9 Å resolution) and itshows that the herbicide-binding site adopts a folded state even in the absence of an inhibitor...
May 9, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28470874/functional-interaction-and-structural-characteristics-of-unique-components-of-helicobacter-pylori-t4ss
#14
REVIEW
Enrique Merino, Marcos Flores-Encarnación, Germán Rubén Aguilar-Gutiérrez
The Helicobacter pylori infection of the human gastric mucosa causes chronic active gastritis and peptic ulcers and is associated with the development of gastric cancer. Epidemiological studies show that these gastric diseases are related to virulent H. pylori strains that harbor the cag pathogenicity island (cag PAI). The cag PAI is a DNA insertion in the H. pylori chromosome that encodes approximately twenty-seven proteins, including the oncoprotein CagA. Approximately twenty of these proteins have been designated as cag type IV secretion system (T4SS) components...
May 4, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28467684/cardiac-contractility-motor-function-and-cross-bridge-kinetics-in-n47k-rlc-mutant-mice
#15
Li Wang, Katarzyna Kazmierczak, Chen-Ching Yuan, Sunil Yadav, Masataka Kawai, Danuta Szczesna-Cordary
We have investigated the physiology and mechanical profiles of skinned papillary muscle fibers from transgenic mice expressing the N47K mutation in the myosin regulatory light chain (RLC), shown to cause hypertrophic cardiomyopathy in humans. The results were compared with wild-type (WT) mice, both expressing the human ventricular RLC. Rate constants of a cross-bridge (XB) cycle were deduced from tension transients induced by sinusoidal length changes during maximal Ca(2+) activation, and were studied as a function of MgATP, MgADP, and Pi concentrations...
May 3, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28467675/ribosome-bound-pub1-modulates-stop-codon-decoding-during-translation-termination-in-yeast
#16
Valery N Urakov, Olga V Mitkevich, Irina V Safenkova, Michael D Ter-Avanesyan
In eukaryotes termination of translation is controlled by polypeptide chain release factors eRF1 and eRF3, of which the former recognizes nonsense codons, while the latter interacts with eRF1 and stimulates polypeptide release from the ribosome in a GTP- dependent manner, and ABCE1, which facilitates ribosome recycling. In this work we demonstrate that Pub1, a yeast protein known to be involved in stress granule formation, regulation of gene expression, and organization of the tubulin cytoskeleton, also plays a role in translation termination...
May 3, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28467668/oxidative-stress-in-malaria-and-artemisinin-combination-therapy-pros-and-cons
#17
REVIEW
Reginald A Kavishe, Jan B Koenderink, Michael Alifrangis
Artemisinin-based combination therapy (ACT) has been adopted as a strategy to mitigate multidrug resistance to antimalarial monotherapies. ACT combines the rapid and effective but rather short plasma half-life antimalarial action of an artemisinin derivative with a longer acting partner drug. Although the exact mechanisms of action of artemisinins is not well understood, several studies have proposed multiple cellular targets of artemisinins with involvement of reactive oxygen species (ROS). Most of the currently used ACT partner drugs are also known to involve ROS production in their mechanisms of action...
May 3, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28467637/n-glycosylation-of-the-%C3%AE-2-adrenergic-receptor-regulates-receptor-function-by-modulating-dimerization
#18
Xiaona Li, Mang Zhou, Wei Huang, Huaiyu Yang
N-glycosylation is a common post-translational modification of G protein-coupled receptors (GPCRs). However, it remains unknown how N-glycosylation affects GPCR signaling. β2 adrenergic receptor (β2 AR) has three N-glycosylation sites: Asn6, Asn15 at the N-terminus and Asn187 at the second extracellular loop (ECL2). Here we show that deletion of the N-glycan did not affect receptor expression and ligand binding. Deletion of the N-glycan at the N-terminus rather than Asn187 showed decreased effects on isoproterenol-promoted G protein dependent signaling, β-arrestin2 recruitment and receptor internalization...
May 3, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28457024/conserved-nucleolar-stress-at-the-onset-of-cell-death
#19
REVIEW
Pierre Golstein
Cell death pervasiveness among multicellular eukaryotes suggested that some core steps of cell death may be conserved. This could be addressed by comparing the course of cell death in organisms belonging to distinct eukaryotic kingdoms. A search for early cell death events in a protist revealed nucleolar disorganization similar to the nucleolar stress often reported in dying animal cells. This indicated a conserved role for the nucleolus at the onset of eukaryotic cell death and leads one to consider the course of cell death as a succession of unequally conserved modules...
April 29, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28457020/virus-host-interplay-in-hepatitis-b-virus-infection-and-epigenetic-treatment-strategies
#20
REVIEW
Kai O Hensel, Julio C Rendon, Maria-Cristina Navas, Marianne G Rots, Jan Postberg
Worldwide, chronic hepatitis B virus (HBV) infection is a major health problem and no cure exists. Importantly, hepatocyte intrusion by HBV particles results in a complex deregulation of both viral and host cellular genetic and epigenetic processes. Among the attempts to develop novel therapeutic approaches against HBV infection, several options targeting the epigenomic regulation of HBV replication are gaining attention. These include the experimental treatment with 'epidrugs'. Moreover, as a targeted approach, the principle of 'epigenetic editing' recently is being exploited to control viral replication...
April 29, 2017: FEBS Journal
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