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https://www.readbyqxmd.com/read/28538735/ensemble-cryo-em-elucidates-the-mechanism-of-translation-fidelity
#1
Anna B Loveland, Gabriel Demo, Nikolaus Grigorieff, Andrei A Korostelev
Gene translation depends on accurate decoding of mRNA, the structural mechanism of which remains poorly understood. Ribosomes decode mRNA codons by selecting cognate aminoacyl-tRNAs delivered by elongation factor Tu (EF-Tu). Here we present high-resolution structural ensembles of ribosomes with cognate or near-cognate aminoacyl-tRNAs delivered by EF-Tu. Both cognate and near-cognate tRNA anticodons explore the aminoacyl-tRNA-binding site (A site) of an open 30S subunit, while inactive EF-Tu is separated from the 50S subunit...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28534666/human-aminoacyl-trna-synthetases-in-diseases-of-the-nervous-system
#2
Jana Ognjenović, Miljan Simonović
Aminoacyl-tRNA synthetases (AaRSs) are ubiquitously expressed enzymes that ensure accurate translation of the genetic information into functional proteins. These enzymes also execute a variety of non-canonical functions that are significant for regulation of diverse cellular processes and that reside outside the realm of protein synthesis. Associations between faults in AaRS-mediated processes and human diseases have been long recognized. Most recent research findings strongly argue that 10 cytosolic and 14 mitochondrial AaRSs are implicated in some form of pathology of the human nervous system...
May 23, 2017: RNA Biology
https://www.readbyqxmd.com/read/28531329/alternative-stable-conformation-capable-of-protein-misinteraction-links-trna-synthetase-to-peripheral-neuropathy
#3
David Blocquel, Sheng Li, Na Wei, Herwin Daub, Mathew Sajish, Maria-Luise Erfurth, Grace Kooi, Jiadong Zhou, Ge Bai, Paul Schimmel, Albena Jordanova, Xiang-Lei Yang
While having multiple aminoacyl-tRNA synthetases implicated in Charcot-Marie-Tooth (CMT) disease suggests a common mechanism, a defect in enzymatic activity is not shared among the CMT-causing mutants. Protein misfolding is a common hypothesis underlying the development of many neurological diseases. Its process usually involves an initial reduction in protein stability and then the subsequent oligomerization and aggregation. Here, we study the structural effect of three CMT-causing mutations in tyrosyl-tRNA synthetase (TyrRS or YARS)...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28526864/a-broad-spectrum-bactericidal-lipopeptide-with-anti-biofilm-properties
#4
Ohad Meir, Fadia Zaknoon, Uri Cogan, Amram Mor
Previous studies of the oligoacyllysyl (OAK) series acyl-lysyl-lysyl-aminoacyl-lysine-amide, suggested their utility towards generating robust linear lipopeptide-like alternatives to antibiotics, although to date, none exhibited potent broad-spectrum bactericidal activity. To follow up on this premise, we produced a new analog (C14KKc12K) and investigated its properties in various media. Mechanistic studies suggest that C14KKc12K uses a non-specific membrane-disruptive mode of action for rapidly reducing viability of Gram-negative bacteria (GNB) similarly to polymyxin B (PMB), a cyclic lipopeptide used as last resort antibiotic...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28525745/conditional-switch-between-frameshifting-regimes-upon-translation-of-dnax-mrna
#5
Neva Caliskan, Ingo Wohlgemuth, Natalia Korniy, Michael Pearson, Frank Peske, Marina V Rodnina
Ribosome frameshifting during translation of bacterial dnaX can proceed via different routes, generating a variety of distinct polypeptides. Using kinetic experiments, we show that -1 frameshifting predominantly occurs during translocation of two tRNAs bound to the slippery sequence codons. This pathway depends on a stem-loop mRNA structure downstream of the slippery sequence and operates when aminoacyl-tRNAs are abundant. However, when aminoacyl-tRNAs are in short supply, the ribosome switches to an alternative frameshifting pathway that is independent of a stem-loop...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28516732/diadenosine-tetraphosphate-ap4a-an-e-coli-alarmone-or-a-damage-metabolite
#6
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/28501621/discovery-of-a-novel-prolyl-trna-synthetase-inhibitor-and-elucidation-of-its-binding-mode-to-the-atp-site-in-complex-with-l-proline
#7
Ryutaro Adachi, Kengo Okada, Robert Skene, Kazumasa Ogawa, Masanori Miwa, Kazuhiro Tsuchinaga, Shoichi Ohkubo, Tsutomu Henta, Tomohiro Kawamoto
Prolyl-tRNA synthetase (PRS) is a member of the aminoacyl-tRNA synthetase family of enzymes and catalyzes the synthesis of prolyl-tRNA(Pro) using ATP, l-proline, and tRNA(Pro) as substrates. An ATP-dependent PRS inhibitor, halofuginone, was shown to suppress autoimmune responses, suggesting that the inhibition of PRS is a potential therapeutic approach for inflammatory diseases. Although a few PRS inhibitors have been derivatized from natural sources or substrate mimetics, small-molecule human PRS inhibitors have not been reported...
May 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28500387/thermal-adaptation-strategies-of-the-extremophile-bacterium-thermus-filiformis-based-on-multi-omics-analysis
#8
F Mandelli, M B Couger, D A A Paixão, C B Machado, C M Carnielli, J A Aricetti, I Polikarpov, R Prade, C Caldana, A F Paes Leme, A Z Mercadante, D M Riaño-Pachón, Fabio Marcio Squina
Thermus filiformis is an aerobic thermophilic bacterium isolated from a hot spring in New Zealand. The experimental study of the mechanisms of thermal adaptation is important to unveil response strategies of the microorganism to stress. In this study, the main pathways involved on T. filiformis thermoadaptation, as well as, thermozymes with potential biotechnological applications were revealed based on omics approaches. The strategy adopted in this study disclosed that pathways related to the carbohydrate metabolism were affected in response to thermoadaptation...
May 12, 2017: Extremophiles: Life Under Extreme Conditions
https://www.readbyqxmd.com/read/28493495/silver-catalyzed-three-component-1-1-aminoacylation-of-homopropargylamines-dual-additions-between-terminal-alkynes-and-isocyanides
#9
Shuo Tong, Cyril Piemontesi, Qian Wang, Mei-Xiang Wang, Jieping Zhu
Reaction of secondary homopropargylamines, isocyanides and water in the presence of a catalytic amount of silver acetate followed by silica gel chromatography purification afforded substituted proline amides in good to excellent yields. Primary homopropargylamines underwent cyclizative Ugi-Joullié three-component reaction with isocyanides and carboxylic acids to afford functionalized N-acyl proline amides. High diastereoselectivity was observed in the synthesis of 4-alkoxy and 4,5-disubstituted proline derivatives...
May 11, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28493438/deficient-activity-of-alanyl-trna-synthetase-underlies-an-autosomal-recessive-syndrome-of-progressive-microcephaly-hypomyelination-and-epileptic-encephalopathy
#10
Tojo Nakayama, Jiang Wu, Patricia Galvin-Parton, Jody Weiss, Mary R Andriola, R Sean Hill, Dylan Vaughan, Malak El-Quessny, Brenda J Barry, Jennifer N Partlow, A James Barkovich, Jiqiang Ling, Ganeshwaran H Mochida
Aminoacyl-transfer RNA (tRNA) synthetases ligate amino acids to specific tRNAs and are essential for protein synthesis. Although alanyl-tRNA synthetase (AARS) is a synthetase implicated in a wide range of neurological disorders from Charcot-Marie-Tooth (CMT) disease to infantile epileptic encephalopathy, there have been limited data on their pathogenesis. Here we report loss-of-function mutations in AARS in two siblings with progressive microcephaly with hypomyelination, intractable epilepsy and spasticity...
May 11, 2017: Human Mutation
https://www.readbyqxmd.com/read/28479486/integrated-diagnosis-project-for-inflammatory-myopathies-an-association-between-autoantibodies-and-muscle-pathology
#11
REVIEW
Shigeaki Suzuki, Akinori Uruha, Norihiro Suzuki, Ichizo Nishino
Inflammatory myopathies are a heterogeneous group of immune-mediated diseases that involve skeletal muscle as well as many other organs. The classification of inflammatory myopathies has been based on clinical diagnoses, pathological diagnoses, and autoantibodies, independently. The clinical phenotypes of inflammatory myopathies are characterized by various autoantibodies that are originally detected by RNA or protein immunoprecipitation. However, since the correlation between histological features and autoantibodies had not been fully elucidated, we created the "Integrated Diagnosis Project for Inflammatory Myopathies" in October 2010...
May 4, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28461832/new-insights-into-antisynthetase-syndrome
#12
Cojocaru Manole, Cojocaru Inimioara Mihaela, Chicos Bogdan
Antisynthetase syndrome (ASS) is a rare chronic autoimmune disorder (2-3 times more common in women than in men), associated with interstitial lung disease (the most important feature), dermatomyositis (DM), and polymyositis (PM). The cause of ASS is unknown. Recent developments in immunology have improved our knowledge and it is now possible to classify ASS according to the presence of myositis specific autoantibodies. The hallmark of ASS is the presence of serum autoantibodies directed against aminoacyl-tRNA synthetases (anti-ARS involved in protein synthesis)...
June 2016: Mædica
https://www.readbyqxmd.com/read/28461123/the-long-term-outcome-of-interstitial-lung-disease-with-anti-aminoacyl-trna-synthetase-antibodies
#13
Kiminobu Tanizawa, Tomohiro Handa, Ran Nakashima, Takeshi Kubo, Yuji Hosono, Kizuku Watanabe, Kensaku Aihara, Kohei Ikezoe, Akihiko Sokai, Yoshinari Nakatsuka, Yoshio Taguchi, Kazuhiro Hatta, Satoshi Noma, Yoichiro Kobashi, Akihiko Yoshizawa, Toru Oga, Toyohiro Hirai, Kazuo Chin, Sonoko Nagai, Takateru Izumi, Tsuneyo Mimori, Michiaki Mishima
RATIONALE: Anti-aminoacyl transfer RNA synthetase antibodies (anti-ARS) are a group of myositis-specific autoantibodies that are detected in the sera of patients with polymyositis and dermatomyositis (PM/DM) and also in those of patients with idiopathic interstitial pneumonias without any connective tissue disease (CTD), including PM/DM. Although we reported the clinical characteristics of interstitial lung disease with anti-ARS antibodies (ARS-ILD) with and without PM/DM, the long-term prognosis of ARS-ILD remains undetermined...
April 15, 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/28457551/short-communication-comparative-proteomic-analysis-of-the-lactating-and-nonlactating-bovine-mammary-gland
#14
W T Dai, Q J Wang, Y X Zou, R R White, J X Liu, H Y Liu
The objective of this study was to determine how bovine mammary protein profiles vary during lactation and the dry period. Three lactating and 3 nonlactating cows were selected for mammary gland tissue sampling. Compared with the mammary proteins in nonlactating cows, a total of 60 differentially expressed proteins (DEP, including 57 upregulated and 3 downregulated) were identified in lactating cows using 2-dimensional difference gel electrophoresis combined with mass spectrometry. These DEP included enzymes and proteins associated with various macromolecular metabolic processes, and appeared to promote the increased metabolic activity associated with milk synthesis and secretion...
April 27, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28455447/acetylation-of-lysine-%C3%AF%C2%B5-amino-groups-regulates-aminoacyl-trna-synthetase-activity-in-escherichia-coli
#15
Qing Ye, Quan-Quan Ji, Wei Yan, Fang Yang, En-Duo Wang
Previous proteomic analyses have shown that aminoacyl-tRNA synthetases (aaRSs) in many organisms can be modified by acetylation of lysine (Lys). In this present study, leucyl-tRNA synthetase and arginyl-tRNA synthetase from Escherichia coli (EcLeuRS and EcArgRS) were overexpressed and purified, and found to be acetylated on Lys residues by mass spectrometry (MS). Glutamine (Gln) scanning mutagenesis revealed that Lys619, Lys624 and Lys809 in EcLeuRS and Lys126 and Lys408 in EcArgRS might play important roles in enzyme activity...
April 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28453527/altered-nucleocytoplasmic-proteome-and-transcriptome-distributions-in-an-in-vitro-model-of-amyotrophic-lateral-sclerosis
#16
Jee-Eun Kim, Yoon Ho Hong, Jin Young Kim, Gye Sun Jeon, Jung Hee Jung, Byung-Nam Yoon, Sung-Yeon Son, Kwang-Woo Lee, Jong-Il Kim, Jung-Joon Sung
Aberrant nucleocytoplasmic localization of proteins has been implicated in many neurodegenerative diseases. Evidence suggests that cytoplasmic mislocalization of nuclear proteins such as transactive response DNA-binding protein 43 (TDP-43) and fused in sarcoma (FUS) may be associated with neurotoxicity in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. This study investigated the changes in nucleocytoplasmic distributions of the proteome and transcriptome in an in vitro model of ALS...
2017: PloS One
https://www.readbyqxmd.com/read/28451794/comparison-of-long-term-prognosis-and-relapse-of-dermatomyositis-complicated-with-interstitial-pneumonia-according-to-autoantibodies-anti-aminoacyl-trna-synthetase-antibodies-versus-anti-melanoma-differentiation-associated-gene-5-antibody
#17
Kentaro Isoda, Takuya Kotani, Tohru Takeuchi, Takao Kiboshi, Kenichiro Hata, Takaaki Ishida, Kenichiro Otani, Takao Kamimori, Hiroshi Fujiwara, Takeshi Shoda, Shigeki Makino
The aim of this study was to investigate long-term prognosis and relapse of dermatomyositis complicated with interstitial pneumonia (DMIP) according to anti-aminoacyl tRNA synthetase (ARS) antibodies and anti-melanoma differentiation-associated gene 5 (MDA5) antibody. This retrospective study comprised 36 patients with DMIP who were divided into the anti-ARS antibody-positive group (ARS+) (n = 12), anti MDA5 antibody-positive group (MDA5+) (n = 11), double-negative group (ARS-/MDA5-) (n = 11), and double-positive group (ARS+/MDA5+) (n = 1)...
April 27, 2017: Rheumatology International
https://www.readbyqxmd.com/read/28451254/fluorogenic-protein-labeling-using-a-genetically-encoded-unstrained-alkene
#18
X Shang, X Song, C Faller, R Lai, H Li, R Cerny, W Niu, J Guo
We developed a new fluorogenic bioorthogonal reaction that is based on the inverse electron-demand Diels-Alder reaction between styrene (an unstrained alkene) and a simple tetrazine. The reaction forms a new fluorophore with no literature precedent. We have identified an aminoacyl-tRNA synthetase/tRNA pair for the efficient and site-specific incorporation of a styrene-containing amino acid into proteins in response to amber nonsense codon. Fluorogenic labeling of purified proteins and intact proteins in live cells were demonstrated...
February 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28437082/high-efficiency-1-and-2-ribosomal-frameshiftings-revealed-by-force-spectroscopy
#19
Te-Wei Tsai, Haopeng Yang, Heng Yin, Shoujun Xu, Yuhong Wang
Ribosomal frameshifting is a rare but ubiquitous process that is being studied extensively. Meanwhile, frameshifting motifs without any secondary mRNA structures were identified but rarely studied experimentally. We report unambiguous observation of highly efficient "-1" and "-2" frameshiftings on a GA7G slippery mRNA without the downstream secondary structure, using force-induced remnant magnetization spectroscopy combined with unique probing schemes. The result represents the first experimental evidence of multiple frameshifting steps...
May 2, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28422494/genetically-encoded-2-aryl-5-carboxytetrazoles-for-site-selective-protein-photo-cross-linking
#20
Yulin Tian, Marco Paolo Jacinto, Yu Zeng, Zhipeng Yu, Jun Qu, Wenshe R Liu, Qing Lin
The genetically encoded photo-cross-linkers promise to offer a temporally controlled tool to map transient and dynamic protein-protein interaction complexes in living cells. Here we report the synthesis of a panel of 2-aryl-5-carboxytetrazole-lysine analogs (ACTKs) and their site-specific incorporation into proteins via amber codon suppression in Escherichia coli and mammalian cells. Among five ACTKs investigated, N-methylpyrroletetrazole-lysine (mPyTK) was found to give robust and site-selective photo-cross-linking reactivity in E...
May 3, 2017: Journal of the American Chemical Society
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