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N-end rule

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https://www.readbyqxmd.com/read/29401302/a-gatekeeper-residue-of-clps1-from-arabidopsis-thaliana-chloroplasts-determines-its-affinity-towards-substrates-of-the-bacterial-n-end-rule
#1
Clara V Colombo, Germán L Rosano, Axel Mogk, Eduardo A Ceccarelli
Proteins that are to be eliminated must be proficiently recognized by proteolytic systems so that inadvertent elimination of useful proteins is avoided. One mechanism to ensure proper recognition is the presence of N-terminal degradation signals (N-degrons) that are targeted by adaptor proteins (N-recognins). The members of the ClpS family of N-recognins identify targets bearing an N-terminal phenylalanine, tyrosine, tryptophan or leucine residue and then, present them to a protease system. This process is known as the "bacterial N-end rule...
February 1, 2018: Plant & Cell Physiology
https://www.readbyqxmd.com/read/29386393/identification-of-wiskott-aldrich-syndrome-protein-wasp-binding-sites-on-the-branched-actin-filament-nucleator-arp2-3-complex
#2
Qing Luan, Alex Zelter, Michael J MacCoss, Trisha N Davis, Brad J Nolen
Arp2/3 complex nucleates branched actin filaments important for cellular motility and endocytosis. WASP family proteins are Arp2/3 complex activators that play multiple roles in branching nucleation, but little is known about the structural bases of these WASP functions, owing to an incomplete understanding of how WASP binds Arp2/3 complex. Recent data show WASP binds two sites, and biochemical and structural studies led to models in which the WASP C segment engages the barbed ends of the Arp3 and Arp2 subunits while the WASP A segment binds the back side of the complex on Arp3...
January 31, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29345112/low-nt-probnp-levels-in-overweight-and-obese-patients-do-not-rule-out-a-diagnosis-of-heart-failure-with-preserved-ejection-fraction
#3
Leo F Buckley, Justin M Canada, Marco G Del Buono, Salvatore Carbone, Cory R Trankle, Hayley Billingsley, Dinesh Kadariya, Ross Arena, Benjamin W Van Tassell, Antonio Abbate
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome that presents clinicians with a diagnostic challenge. The use of natriuretic peptides to exclude a diagnosis of HFpEF has been proposed. We sought to compare HFpEF patients with N-terminal pro-brain natriuretic peptide (NT-proBNP) level above and below the proposed cut-off. METHODS: Stable patients (n = 30) with left ventricular (LV) ejection fraction ≥ 50% were eligible if they had a diagnosis of HF according to the European Society of Cardiology diagnostic criteria...
January 18, 2018: ESC Heart Failure
https://www.readbyqxmd.com/read/29319709/displacement-of-%C3%AE-5-cyclopentadienyl-ligands-from-half-sandwich-c-c-nhc-cyanoalkyl-nickel-ii-metallacycles-further-insight-into-the-structure-of-the-resulting-cp-free-nickelacycles-and-a-catalytic-activity-study
#4
Bernardo de P Cardoso, Jean-Marie Bernard-Schaaf, Saurabh Shahane, Luis F Veiros, Michael J Chetcuti, Vincent Ritleng
Four cationic C,C-(NHC-cyanoalkyl)-nickel(ii) metallacyclic complexes, [Ni{Me-NHC-CH2CH(CN)}(NCMe)](PF6) (2a), [Ni{Mes-NHC-CH2CH(CN)}(NCMe)](PF6) (2b), [Ni{Mes-NHC-(CH2)2CH(CN)}(NCMe)](PF6) (2c) and [Ni{DiPP-NHC-(CH2)2CH(CN)}(NCMe)](PF6) (2d), were prepared by the removal of the Cp ligand under acidic conditions at 0 °C from the corresponding half-sandwich nickelacycles [NiCp{R-NHC-(CH2)nCH(CN)}] (1a-1d; Cp = η5-C5H5; n = 1 or 2; R-NHC-(CH2)nCH(CN) = 1-R-3-[(CH2)nCH(CN)]-imidazol-2-ylidene). Full characterization of 2a-d by 1H and 13C{1H} NMR spectroscopy in CD3CN and pyridine-d5, ATR-FTIR spectroscopy, mass spectrometry, and CHN microanalyses established the presence of only one acetonitrile ligand per nickel atom in the solid state...
January 10, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29301968/engineering-posttranslational-proofreading-to-discriminate-nonstandard-amino-acids
#5
Aditya M Kunjapur, Devon A Stork, Erkin Kuru, Oscar Vargas-Rodriguez, Matthieu Landon, Dieter Söll, George M Church
Incorporation of nonstandard amino acids (nsAAs) leads to chemical diversification of proteins, which is an important tool for the investigation and engineering of biological processes. However, the aminoacyl-tRNA synthetases crucial for this process are polyspecific in regard to nsAAs and standard amino acids. Here, we develop a quality control system called "posttranslational proofreading" to more accurately and rapidly evaluate nsAA incorporation. We achieve this proofreading by hijacking a natural pathway of protein degradation known as the N-end rule, which regulates the lifespan of a protein based on its amino-terminal residue...
January 4, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29301343/the-neonatal-intensive-care-unit-environmental-stressors-and-supports
#6
Kristen G Williams, Kayla T Patel, Julie M Stausmire, Christy Bridges, Mary W Mathis, Jennifer L Barkin
The relationship between maternal mental health and infant development has been established in the literature. The Neonatal Intensive Care Unit (NICU) is a particularly challenging environment for new mothers as several natural processes are disrupted. The objective of this study is to elucidate protective factors and environmental deficits associated with the NICU. The experiences of forty-six (n = 46) mothers of infants admitted to a Level III NICU in the Midwestern United States, who responded to a related open-ended question, were analyzed thematically...
January 3, 2018: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/29295953/the-endoplasmic-reticulum-residing-chaperone-bip-is-short-lived-and-metabolized-through-n-terminal-arginylation
#7
Sang Mi Shim, Ha Rim Choi, Ki Woon Sung, Yoon Jee Lee, Sung Tae Kim, Daeho Kim, Su Ran Mun, Joonsung Hwang, Hyunjoo Cha-Molstad, Aaron Ciechanover, Bo Yeon Kim, Yong Tae Kwon
BiP and other endoplasmic reticulum (ER)-resident proteins are thought to be metabolically stable and to function primarily in the ER lumen. We sought to assess how the abundance of these proteins dynamically fluctuates in response to various stresses and how their subpopulations are relocated to non-ER compartments such as the cytosol. We showed that the molecular chaperone BiP (also known as GRP78) was short-lived under basal conditions and ER stress. The turnover of BiP was in part driven by its amino-terminal arginylation (Nt-arginylation) by the arginyltransferase ATE1, which generated an autophagic N-degron of the N-end rule pathway...
January 2, 2018: Science Signaling
https://www.readbyqxmd.com/read/29284905/application-of-ethics-for-providing-telemedicine-services-and-information-technology
#8
REVIEW
Mostafa Langarizadeh, Fatemeh Moghbeli, Ali Aliabadi
Introduction: Advanced technology has increased the use of telemedicine and Information Technology (IT) in treating or rehabilitating diseases. An increased use of technology increases the importance of the ethical issues involved. The need for keeping patients' information confidential and secure, controlling a number of therapists' inefficiency as well as raising the quality of healthcare services necessitates adequate heed to ethical issues in telemedicine provision. Aim: The goal of this review is gathering all articles that are published through 5 years until now (2012-2017) for detecting ethical issues for providing telemedicine services and Information technology...
October 2017: Medical Archives
https://www.readbyqxmd.com/read/29275195/nitric-oxide-mediated-integrative-alterations-in-plant-metabolism-to-confer-abiotic-stress-tolerance-no-crosstalk-with-phytohormones-and-no-mediated-post-translational-modifications-in-modulating-diverse-plant-stress
#9
REVIEW
Fareen Sami, Mohammad Faizan, Ahmad Faraz, Husna Siddiqui, Mohammad Yusuf, Shamsul Hayat
Nitric oxide (NO) is a major signaling biomolecule associated with signal transduction in plants. The beneficial role of NO in plants, exposed to several abiotic stresses shifted our understanding as it being not only free radical, released from the toxic byproducts of oxidative metabolism but also helps in plant sustenance. An explosion of research in plant NO biology during the last two decades has revealed that NO is a key signal associated with plant growth, germination, photosynthesis, leaf senescence, pollen growth and reorientation...
December 21, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/29261001/regulation-of-autophagic-proteolysis-by-the-n-recognin-sqstm1-p62-of-the-n-end-rule-pathway
#10
Hyunjoo Cha-Molstad, Su Hyun Lee, Jung Gi Kim, Ki Woon Sung, Joonsung Hwang, Sang Mi Shim, Srinivasrao Ganipisetti, Terry McGuire, Inhee Mook-Jung, Aaron Ciechanover, Xiang-Qun Xie, Bo Yeon Kim, Yong Tae Kwon
In macroautophagy/autophagy, cargoes are collected by specific receptors, such as SQSTM1/p62 (sequestosome 1), and delivered to phagophores for lysosomal degradation. To date, little is known about how cells modulate SQSTM1 activity and autophagosome biogenesis in response to accumulating cargoes. In this study, we show that SQSTM1 is an N-recognin whose ZZ domain binds N-terminal arginine (Nt-Arg) and other N-degrons (Nt-Lys, Nt-His, Nt-Trp, Nt-Phe, and Nt-Tyr) of the N-end rule pathway. The substrates of SQSTM1 include the endoplasmic reticulum (ER)-residing chaperone HSPA5/GRP78/BiP...
December 20, 2017: Autophagy
https://www.readbyqxmd.com/read/29235689/adduction-of-ammonium-to-polylactides-to-modify-their-dissociation-behavior-in-cid
#11
Christophe Chendo, Trang N T Phan, Marion Rollet, Didier Gigmes, Laurence Charles
RATIONALE: The goal of this work was to modify dissociation pathways of polylactide (PLA) holding benzyl and hydroxyl terminations, in order to circumvent coincidence of product ions generated during collisional activation of sodiated chains, which prevented their reliable characterization. METHODS: Benzyl-, hydroxyl-terminated PLAs were ionized as ammonium adducts in positive ion mode electrospray and subjected to collision-induced dissociation (CID). MS/MS experiments were conducted in a Q-TOF instrument for safe assignment of product ions based on their elemental composition derived from accurate mass measurements...
December 13, 2017: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/29233616/n-term-2017-proteostasis-via-the-n-terminus
#12
Nico Dissmeyer, Emmanuelle Graciet, Michael J Holdsworth, Daniel J Gibbs
N-term 2017 was the first international meeting to bring together researchers from diverse disciplines with a shared interest in protein N-terminal modifications and the N-end rule pathway of ubiquitin-mediated proteolysis, providing a platform for interdisciplinary cross-kingdom discussions and collaborations, as well as strengthening the visibility of this growing scientific community.
December 9, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29231806/a-picorna-like-virus-suppresses-the-n-end-rule-pathway-to-inhibit-apoptosis
#13
Zhaowei Wang, Xiaoling Xia, Xueli Yang, Xueyi Zhang, Yongxiang Liu, Di Wu, Yuan Fang, Yujie Liu, Jiuyue Xu, Yang Qiu, Xi Zhou
The N-end rule pathway is an evolutionarily conserved proteolytic system that degrades proteins containing N-terminal degradation signals called N-degrons, and has emerged as a key regulator of various processes. Viruses manipulate diverse host pathways to facilitate viral replication and evade antiviral defenses. However, it remains unclear if viral infection has any impact on the N-end rule pathway. Here, using a picorna-like virus as a model, we found that viral infection promoted the accumulation of caspase-cleaved Drosophila Inhibitor of Apoptosis 1 (DIAP1) by inducing the degradation of N-terminal amidohydrolase 1 (NTAN1), a key N-end rule component that identifies N-degron to initiate the process...
December 12, 2017: ELife
https://www.readbyqxmd.com/read/29208888/polyarthritis-is-a-rare-manifestation-of-pachydermoperiostosis-a-case-report
#14
M F Ahmmed, M N Shazzad, S Ferdous, A K Azad, S A Haq
Pachydermoperiostosis or primary hypertrophic osteoarthropathy, also known as Touraine-Solente-Gole syndrome, is a rare process, frequently inherited. In its complete form it is characterized by pachydermia (thickening of the skin), skeletal changes (periostosis) and acropachia (digital clubbing). Diagnosis can be made considering the typical clinical features and the histological feature. We report a patient of 25-year old man presented with joint pain involving in multiple joints for last 7 years and progressive enlargement of his hands and feet with profuse sweating of palms and soles for last 4 years...
October 2017: Mymensingh Medical Journal: MMJ
https://www.readbyqxmd.com/read/29178640/expanding-the-mutational-spectrum-in-johanson-blizzard-syndrome-identification-of-whole-exon-deletions-and-duplications-in-the-ubr1-gene-by-multiplex-ligation-dependent-probe-amplification-analysis
#15
Maja Sukalo, Eva Schäflein, Ina Schanze, David B Everman, Nima Rezaei, Jesús Argente, Isabel Lorda-Sanchez, Charu Deshpande, Tsutomu Takahashi, Alexander Kleger, Martin Zenker
BACKGROUND: Johanson-Blizzard syndrome (JBS, MIM #243800) is a very rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency, nasal wing hypoplasia, hypodontia, and other abnormalities. JBS is caused by mutations of the UBR1 gene (MIM *605981), encoding a ubiquitin ligase of the N-end rule pathway. METHODS: Molecular findings in a total of 65 unrelated patients with a clinical diagnosis of JBS who were previously screened for UBR1 mutations by Sanger sequencing were reviewed and cases lacking a disease-causing UBR1 mutation on either one or both alleles were included in this study...
November 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/29170951/bacterial-genome-editing-strategy-for-control-of-transcription-and-protein-stability
#16
Ida Lauritsen, Virginia Martínez, Carlotta Ronda, Alex Toftgaard Nielsen, Morten H H Nørholm
In molecular biology and cell factory engineering, tools that enable control of protein production and stability are highly important. Here, we describe protocols for tagging genes in Escherichia coli allowing for inducible degradation and transcriptional control of any soluble protein of interest. The underlying molecular biology is based on the two cross-kingdom tools CRISPRi and the N-end rule for protein degradation. Genome editing is performed with the CRMAGE technology and randomization of the translational initiation region minimizes the polar effects of tag insertion...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29168982/n-terminomics-reveals-control-of-arabidopsis-seed-storage-proteins-and-proteases-by-the-arg-n-end-rule-pathway
#17
Hongtao Zhang, Lucy Gannon, Kirsty L Hassall, Michael J Deery, Daniel J Gibbs, Michael J Holdsworth, Renier A L van der Hoorn, Kathryn S Lilley, Frederica L Theodoulou
The N-end rule pathway of targeted protein degradation is an important regulator of diverse processes in plants but detailed knowledge regarding its influence on the proteome is lacking. To investigate the impact of the Arg/N-end rule pathway on the proteome of etiolated seedlings, we used terminal amine isotopic labelling of substrates with tandem mass tags (TMT-TAILS) for relative quantification of N-terminal peptides in prt6, an Arabidopsis thaliana N-end rule mutant lacking the E3 ligase PROTEOLYSIS6 (PRT6)...
November 23, 2017: New Phytologist
https://www.readbyqxmd.com/read/29136445/effect-of-varying-doses-of-epicutaneous-immunotherapy-vs-placebo-on-reaction-to-peanut-protein-exposure-among-patients-with-peanut-sensitivity-a-randomized-clinical-trial
#18
RANDOMIZED CONTROLLED TRIAL
Hugh A Sampson, Wayne G Shreffler, William H Yang, Gordon L Sussman, Terri F Brown-Whitehorn, Kari C Nadeau, Amarjit S Cheema, Stephanie A Leonard, Jacqueline A Pongracic, Christine Sauvage-Delebarre, Amal H Assa'ad, Frederic de Blay, J Andrew Bird, Stephen A Tilles, Franck Boralevi, Thierry Bourrier, Jacques Hébert, Todd D Green, Roy Gerth van Wijk, André C Knulst, Gisèle Kanny, Lynda C Schneider, Marek L Kowalski, Christophe Dupont
Importance: Epicutaneous immunotherapy may have potential for treating peanut allergy but has been assessed only in preclinical and early human trials. Objective: To determine the optimal dose, adverse events (AEs), and efficacy of a peanut patch for peanut allergy treatment. Design, Setting, and Participants: Phase 2b double-blind, placebo-controlled, dose-ranging trial of a peanut patch in peanut-allergic patients (6-55 years) from 22 centers, with a 2-year, open-label extension (July 31, 2012-July 31, 2014; extension completed September 29, 2016)...
November 14, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/29122887/a-reference-based-protein-degradation-assay-without-global-translation-inhibitors
#19
Jang-Hyun Oh, Shun-Jia Chen, Alexander Varshavsky
Although it is widely appreciated that the use of global translation inhibitors, such as cycloheximide, in protein degradation assays may result in artefacts, these inhibitors continue to be employed, owing to the absence of robust alternatives. We describe here the promoter reference technique (PRT), an assay for protein degradation with two advantageous features: a reference protein and a gene-specific inhibition of translation. In PRT assays, one measures, during a chase, the ratio of a test protein to a long-lived reference protein, a dihydrofolate reductase (DHFR)...
November 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29107562/dolutegravir-as-maintenance-monotherapy-for-hiv-domono-a-phase-2-randomised-non-inferiority-trial
#20
Ingeborg Wijting, Casper Rokx, Charles Boucher, Jeroen van Kampen, Suzan Pas, Theodora de Vries-Sluijs, Carolina Schurink, Hannelore Bax, Maarten Derksen, Eleni-Rosalina Andrinopoulou, Marchina van der Ende, Eric van Gorp, Jan Nouwen, Annelies Verbon, Wouter Bierman, Bart Rijnders
BACKGROUND: The high genetic barrier to resistance of dolutegravir might allow for its use as maintenance monotherapy in patients with HIV. We investigated whether dolutegravir monotherapy was non-inferior to combination antiretroviral therapy (ART) for maintaining virological suppression in patients with HIV-1 infection successfully treated with combination ART. METHODS: We did this open-label, phase 2, randomised non-inferiority trial at two medical centres in the Netherlands...
December 2017: Lancet HIV
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