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FEBS Journal

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https://www.readbyqxmd.com/read/28109185/folding-of-intrinsically-disordered-plant-lea-proteins-is-driven-by-glycerol-induced-crowding-and-the-presence-of-membranes
#1
Anne Bremer, Martin Wolff, Anja Thalhammer, Dirk K Hincha
Late embryogenesis abundant (LEA) proteins are related to cellular dehydration tolerance. Most LEA proteins are predicted to have no stable secondary structure in solution, i.e. to be intrinsically disordered proteins (IDPs), but they may acquire α-helical structure upon drying. In the model plant Arabidopsis thaliana the LEA proteins COR15A and COR15B are highly induced upon cold treatment and are necessary for the plants to attain full freezing tolerance. Freezing leads to increased intracellular crowding due to dehydration by extracellular ice crystals...
January 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28109179/quantitative-and-integrative-analysis-of-paracrine-hepatocyte-activation-by-non-parenchymal-cells-upon-lipopolysaccharide-induction
#2
Katharina Beuke, Frank A Schildberg, Federico Pinna, Ute Albrecht, Roman Liebe, Michaela Bissinger, Peter Schirmacher, Steven Dooley, Johannes G Bode, Percy A Knolle, Ursula Kummer, Kai Breuhahn, Sven Sahle
Gut-derived bacterial lipopolysaccharides (LPS) stimulate the secretion of tumor necrosis factor (TNF) from liver macrophages (MCs), liver sinusoidal endothelial cells (LSECs), and hepatic stellate cells (HSCs), which control the acute phase response in hepatocytes through activation of the NF-κB pathway. The individual and cooperative impact of non-parenchymal cells on this clinically relevant response has not been analysed in detail due to technical limitations. To gain an integrative view on this complex inter- and intracellular communication, we combined a multi-scale mathematical model with quantitative, time-resolved experimental data of different primary murine liver cell types...
January 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28109177/glutamine-synthetase-stabilizes-the-binding-of-glnr-to-nitrogen-fixation-gene-operators
#3
Gabriela de Carvalho Fernandes, Ksenia Hauf, Fernando Hayashi Sant'Anna, Karl Forchhammer, Luciane Maria Pereira Passaglia
Biological nitrogen fixation (BNF) is a high energy demanding process carried out by diazotrophic microorganisms that supply combined nitrogen to the biosphere. The genes related to BNF are strictly regulated, but these mechanisms are poorly understood in Gram-positive bacteria. The transcription factor GlnR was proposed to regulate nitrogen fixation related genes based on Paenibacillus comparative genomics. In order to validate this proposal, we investigated BNF regulatory sequences in Paenibacillus riograndensis SBR5(T) genome...
January 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28109174/%C3%AE-%C3%AE-nac-cooperates-with-sam37-to-mediate-early-stages-of-mitochondrial-protein-import
#4
J Carlos Ponce-Rojas, M Clara Avendaño-Monsalve, A Roberto Yañez-Falcón, Fabiola Jaimes-Miranda, Erika Garay, Francisco Torres-Quiroz, Alexander DeLuna, Soledad Funes
The mitochondrial proteome is mostly composed of nuclear-encoded proteins. Such polypeptides are synthesized with signals that guide their intracellular transport to the surface of the organelle and later within the different mitochondrial sub-compartments until they reach their functional destination. It has been suggested that NAC - a cytosolic chaperone which recognizes nascent chains on translationally active ribosomes - has a role in the import of nuclear-encoded mitochondrial proteins. However, the molecular mechanisms that regulate the NAC-mediated co-translational import are still not clear...
January 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28107776/activity-based-probes-for-the-multicatalytic-proteasome
#5
REVIEW
David S Hewings, John A Flygare, Ingrid E Wertz, Matthew Bogyo
Proteasomes are multisubunit protease complexes responsible for degrading most intracellular proteins. In addition to removing damaged proteins, they regulate many important cellular processes through the controlled degradation of transcription factors, cell cycle regulators and enzymes. Eukaryotic proteasomes have three catalytic subunits, β1, β2 and β5, that each have different substrate specificities. Additionally, although we know that diverse cell types express proteasome variants with distinct activity and specificity profiles, the functions of these different pools of proteasomes are not fully understood...
January 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28107769/the-transcriptional-modulator-ifrd1-controls-pgc-1%C3%AE-expression-under-short-term-adrenergic-stimulation-in-brown-adipocytes
#6
Gyujin Park, Tetsuhiro Horie, Takashi Kanayama, Kazuya Fukasawa, Takashi Iezaki, Yuki Onishi, Kakeru Ozaki, Yukari Nakamura, Yukio Yoneda, Takeshi Takarada, Eiichi Hinoi
Sympathetic tone activates the function of classical brown adipocytes, which constitutively exist in the brown adipose tissue, and inducible brown adipocytes (so-called beige adipocytes), which sporadically reside within the white adipose tissue. Here we identified the transcriptional modulator interferon-related developmental regulator 1 (Ifrd1) as a negative regulator of thermogenic and mitochondrial gene expression in brown adipocytes. Ifrd1 expression was markedly induced by cold exposure and administration of CL-316243 (a β3 adrenergic agonist) in interscapular brown adipose and inguinal subcutaneous white adipose tissues, but not in epididymal visceral white adipose tissue, in vivo...
January 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28103425/efficient-synthesis-of-%C3%AE-galactosyl-oligosaccharides-using-a-mutant-bacteroides-thetaiotaomicron-retaining-%C3%AE-galactosidase-btgh97b
#7
Masayuki Okuyama, Kana Matsunaga, Ken-Ichi Watanabe, Keitaro Yamashita, Takayoshi Tagami, Asako Kikuchi, Min Ma, Patcharapa Klahan, Haruhide Mori, Min Yao, Atsuo Kimura
The preparation of a glycosynthase, a catalytic nucleophile mutant of a glycosidase, is a well-established strategy for the effective synthesis of glycosidic linkages. However, glycosynthases derived from α-glycosidases can give poor yields of desired products because they require generally unstable β-glycosyl fluoride donors. Here, we investigate a transglycosylation catalyzed by a catalytic nucleophile mutant derived from a glycoside hydrolase family (GH) 97 α-galactosidase, using more stable β-galactosyl azide and α-galactosyl fluoride donors...
January 19, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28103421/structure-of-the-arabidopsis-thaliana-nadph-cytochrome-p450-reductase-2-atr2-provides-insight-into-its-function
#8
Guoqi Niu, Shun Zhao, Lei Wang, Wei Dong, Lin Liu, Yikun He
Members of the cytochrome P450 family catalyze a variety of monooxygenase reactions, and for the eukaryotic membrane-bound members, NADPH is typically used as the reducing agent. The flavoprotein NADPH-cytochrome P450 reductase (CPR) enables electron transfer from NADPH to cytochrome P450 via its flavin cofactors. ATR2 is one of the two authentic CPR genes in the genome of the model plant Arabidopsis thaliana, and its product has been physiologically and kinetically characterized. Here, we report the 2.3-Å structure of ATR2 and find that the position of the two flavin cofactors differs from that of other known CPR structures...
January 19, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28102934/crosstalk-between-angiotensin-and-the-non-amyloidogenic-pathway-of-alzheimer-s-amyloid-precursor-protein
#9
Anna Maria Kanarek, Annika Wagner, Jim Küppers, Michael Gütschow, Rolf Postina, Elzbieta Kojro
The association between hypertension and an increased risk for Alzheimer's disease (AD) and dementia is well established. Many data suggest that modulation of the renin-angiotensin system may be meaningful for the prevention and therapy of neurodegenerative disorders, in particular AD. Proteolytic cleavage of the amyloid precursor protein (APP) by α-secretase precludes formation of neurotoxic Aβ peptides and is expected to counteract the development of AD. An established approach for the up-regulation of α-secretase cleavage is activation of G protein-coupled receptors (GPCRs)...
January 19, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28079298/from-phosphoproteins-to-phosphoproteomes-a-historical-account
#10
REVIEW
Andrea Venerando, Luca Cesaro, Lorenzo A Pinna
The first phosphoprotein (casein) was discovered in 1883, yet the enzyme responsible for its phosphorylation was identified only 130 years later, in 2012. During the very long time elapsed between these two events, with special reference to the last decades of the 1900s, it became evident that, far from being an oddity, phosphorylation affects the majority of eukaryotic proteins during their lifespan, and that this reaction is catalysed by the members of a large family of protein kinases, susceptible to a variety of stimuli controlling nearly every aspects of life and death...
January 12, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28075071/multi-target-selection-of-catalytic-antibodies-wih-%C3%AE-lactamase-activity-using-phage-display
#11
Melody A Shahsavarian, Nancy Chaaya, Narciso Costa, Didier Boquet, Alexandre Atkinson, Bernard Offmann, Srini V Kaveri, Sébastien Lacroix-Desmazes, Alain Friboulet, Bérangère Avalle, Séverine Padiolleau-Lefèvre
β-lactamase enzymes responsible for bacterial resistance to antibiotics are among the most important health threats to the human population today. Understanding the increasingly vast structural motifs responsible for the catalytic mechanism of β-lactamases will help improve the future design of new generation antibiotics and mechanism-based inhibitors of these enzymes. Here we report the construction of a large murine scFv phage display library of size 2.7×10(9) with extended diversity by combining different mouse models...
January 11, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28075068/binding-and-processing-of-%C3%AE-lactam-antibiotics-by-the-transpeptidase-ldtmt2-from-mycobacterium-tuberculosis
#12
Eva Maria Steiner, Gunter Schneider, Robert Schnell
β-lactam antibiotics represent a novel direction in the chemotherapy of tuberculosis that brings the peptidoglycan layer of the complex mycobacterial cell wall in focus as therapeutic target. Peptidoglycan stability in Mycobacterium tuberculosis especially during infection relies on the non-conventional peptide cross-links formed by L,D-transpeptidases. These enzymes are known to be inhibited by β-lactams, primarily carbapenems, leading to a stable covalent modification at the enzyme active site. A panel of sixteen β-lactams antibiotics was characterized by inhibition kinetics, mass spectrometry and x-ray crystallography to identify efficient compounds and study their action on the essential transpeptidase LdtMt2 ...
January 11, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28075062/specific-arabidopsis-thaliana-malic-enzyme-isoforms-can-provide-anaplerotic-pyruvate-carboxylation-function-in-saccharomyces-cerevisiae
#13
Mariana Beatriz Badia, Robert Mans, Alicia V Lis, Marcos Ariel Tronconi, Cintia Lucía Arias, Verónica Graciela Maurino, Carlos Santiago Andreo, María Fabiana Drincovich, Antonius J A van Maris, Mariel Claudia Gerrard Wheeler
NAD(P)-malic enzyme (NAD(P)-ME) catalyzes the reversible oxidative decarboxylation of malate to pyruvate, CO2 and NAD(P)H and is present as a multigene family in Arabidopsis. The carboxylation reaction catalyzed by purified recombinant A. thaliana NADP-ME proteins is faster than those reported for other animal or plant isoforms. In contrast, no carboxylation activity could be detected in vitro for the NAD-dependent counterparts. In order to further investigate their putative carboxylating role in vivo, Arabidopsis NAD(P)-ME isoforms, as well as the NADP-ME2del2 (with a decreased ability to carboxylate pyruvate) and NADP-ME2R115A (lacking fumarate activation) versions, were functionally expressed in the cytosol of pyruvate carboxylase negative (Pyc(-) ) Saccharomyces cerevisiae strains...
January 11, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28075056/m1-aminopeptidases-as-drug-targets-broad-applications-or-therapeutic-niche
#14
REVIEW
Nyssa Drinkwater, Jisook Lee, Wei Yang, Tess R Malcolm, Sheena McGowan
M1 aminopeptidase enzymes are a diverse family of metalloenzymes characterized by conserved structure and reaction specificity. Excluding viruses, M1 aminopeptidases are distributed throughout all phyla, and have been implicated in a wide range of functions including cell maintenance, growth and development, and defense. The structure and catalytic mechanism of M1 aminopeptidases are well understood, and make them ideal candidates for the design of small molecule inhibitors. As a result, many research groups have assessed their utility as therapeutic targets for both infectious and chronic diseases of humans, and many inhibitors with a range of target specificities and potential therapeutic applications have been developed...
January 11, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28075055/argonaute-2-immunoprecipitation-revealed-lats1-as-a-novel-pro-apoptotic-target-of-mir-21-in-t-cells
#15
Nato Teteloshvili, Katarzyna Smigielska-Czepiel, Ye Yuan, Annika Seitz, Debora de Jong, Bea Rutgers, Pytrick Jellema, Roelof Jan van der Lei, Izabella Slezak-Prochazka, Elisabeth Brouwer, Annemieke M H Boots, Bart-Jan Kroesen, Anke van den Berg, Joost Kluiver
MicroRNA (miR)-21 is an important suppressor of T-cell apoptosis that is also overexpressed in many types of cancers. The exact mechanisms underlying the anti-apoptotic effects of miR-21 are not well understood. In this study, we used the Jurkat T-cell line as a model to identify apoptosis-associated miR-21 target genes. We showed that expression of miR-21 rapidly increases upon αCD3/αCD28 activation of Jurkat cells. Inhibition of miR-21 reduced cell growth which could be explained by an increase in apoptosis...
January 11, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28064468/the-membrane-activity-of-bok-involves-formation-of-large-stable-toroidal-pores-and-is-promoted-by-cbid
#16
Yuniel Fernández-Marrero, Stephanie Bleicken, Kushal Kumar Das, Daniel Bachmann, Thomas Kaufmann, Ana J Garcia-Saez
The BCL-2 family members are key regulators of the intrinsic apoptotic pathway, which is defined by permeabilisation of the mitochondrial outer membrane by members of the BAX-like subfamily. BOK is classified as a BAX-like protein; however, its (patho-)physiological role remains largely unclear. We therefore assessed the membrane permeabilisation potential of C-terminally truncated recombinant BOK, BOK(∆C) . We show that BOK(∆C) can permeabilize liposomes mimicking the composition of mitochondrial outer membrane, but not of endoplasmic reticulum, forming large and stable pores over time...
January 8, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28064438/integration-of-cellular-ubiquitin-and-membrane-traffic-systems-focus-on-deubiquitylases
#17
REVIEW
Michael J Clague, Sylvie Urbé
The cell is comprised of integrated multi-level protein networks or systems. The ubiquitin, protein homeostasis and membrane trafficking systems are highly integrated. Here we look at the influence of reversible ubiquitylation on membrane trafficking and organelle dynamics. We review the regulation of endocytic sorting, selective autophagy and the secretory pathway by ubiquitin signals, with a particular focus on detailing the contribution of deubiquitylating enzymes. This article is protected by copyright...
January 8, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28060464/rna-polymerase-ii-components-and-rrn7-form-a-pre-initiation-complex-on-the-homold-box-to-promote-ribosomal-protein-gene-expression-in-schizosaccharomyces-pombe
#18
Matías Montes, Sandra Moreira-Ramos, Diego A Rojas, Fabiola Urbina, Norbert F Käufer, Edio Maldonado
In Schizosaccharomyces pombe, ribosomal protein gene (RPG) promoters contain a TATA box analog, the HomolD box, which is bound by the Rrn7 protein. Despite the importance of ribosome biogenesis for cell survival, the mechanisms underlying RPG transcription remain unknown. In this study, we found that components of the RNA polymerase II (RNAPII) system, consisting of the initiation or general transcription factors (GTFs) TFIIA, IIB, IIE, TBP and the RNAPII holoenzyme, interacted directly with Rrn7 in vitro and were able to form a pre-initiation complex (PIC) on the HomolD box...
January 6, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28054745/the-discovery-of-alzheimer-causing-mutations-in-the-app-gene-and-the-formulation-of-the-amyloid-cascade-hypothesis
#19
REVIEW
John Hardy
The cloning of APP and genetic analysis of families with Alzheimer's disease were both reported in 1987 and much present work on the disease is based upon the foundations laid at that time. Progress was not smooth however, and many errors were made. In this memoir, I lay out both the progress and the errors. This article is protected by copyright. All rights reserved.
January 5, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28054744/the-crystal-structure-of-pkni-from-mycobacterium-tuberculosis-shows-an-inactive-pseudokinase-like-conformation
#20
María-Natalia Lisa, Tristan Wagner, Matthieu Alexandre, Nathalie Barilone, Bertrand Raynal, Pedro M Alzari, Marco Bellinzoni
Eukaryotic-like Ser/Thr protein kinases (ePKs) have been identified in many bacterial species, where they are known to mediate signalling mechanisms that share several features with their eukaryotic counterparts. In Mycobacterium tuberculosis, PknI is one of the eleven predicted ePKs and it has been related to bacterial virulence. In order to better understand the molecular basis of its role in mycobacterial signalling, we solved the crystal structure of the PknI cytoplasmic domain. We found that even though PknI possesses most conserved elements characteristic of Hanks-type kinases, it is degraded in several motifs that are essential for the ePKs catalytic activity...
January 5, 2017: FEBS Journal
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