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https://www.readbyqxmd.com/read/28823056/exploiting-non-canonical-translation-to-identify-new-targets-for-t-cell-based-cancer-immunotherapy
#1
REVIEW
Céline M Laumont, Claude Perreault
Cryptic MHC I-associated peptides (MAPs) are produced via two mechanisms: translation of protein-coding genes in non-canonical reading frames and translation of allegedly non-coding sequences. In general, cryptic MAPs are coded by relatively short open reading frames whose translation can be regulated at the level of initiation, elongation or termination. In contrast to conventional MAPs, the processing of cryptic MAPs is frequently proteasome independent. The existence of cryptic MAPs derived from allegedly non-coding regions enlarges the scope of CD8 T cell immunosurveillance from a mere ~2% to as much as ~75% of the human genome...
August 19, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28823028/backbone-resonance-assignments-of-complexes-of-human-voltage-dependent-sodium-channel-nav1-2-iq-motif-peptide-bound-to-apo-calmodulin-and-to-the-c-domain-fragment-of-apo-calmodulin
#2
Ryan Mahling, Adina M Kilpatrick, Madeline A Shea
Human voltage-gated sodium channel NaV1.2 has a single pore-forming α-subunit and two transmembrane β-subunits. Expressed primarily in the brain, NaV1.2 is critical for initiation and propagation of action potentials. Milliseconds after the pore opens, sodium influx is terminated by inactivation processes mediated by regulatory proteins including calmodulin (CaM). Both calcium-free (apo) CaM and calcium-saturated CaM bind tightly to an IQ motif in the C-terminal tail of the α-subunit. Our thermodynamic studies and solution structure (2KXW) of a C-domain fragment of apo (13)C,(15)N- CaM (CaMC) bound to an unlabeled peptide with the sequence of rat NaV1...
August 19, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28822865/formation-and-morphogenesis-of-a-cuttlebone-s-aragonite-biomineral-structures-for-the-common-cuttlefish-sepia-officinalis-on-the-nanoscale-revisited
#3
Vida Čadež, Srečo D Škapin, Adrijana Leonardi, Igor Križaj, Saša Kazazić, Branka Salopek-Sondi, Ivan Sondi
This study describes and examines the structural and morphological properties of the hierarchically organized, aragonite cuttlebone forms for the common cuttlefish (Sepia officinalis, L.), including its main structural parts, the dorsal shield, and the chambers. Specifically, it complements the mechanism for the self-organized formation of aragonite, identifies the presence, and determines the role of soluble organic matrix (SOM) proteins in the morphogenesis of the cuttlebone's biomineral structures on the nanoscale...
August 10, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28822817/rosiglitazone-promotes-cardiac-hypertrophy-and-alters-chromatin-remodeling-in-isolated-cardiomyocytes
#4
Lama Fawaz Pharaon, Naglaa Fathi El-Orabi, Muhammad Kunhi, Nadya Al Yacoub, Salma Mahmoud Awad, Coralie Poizat
Rosiglitazone is an anti-diabetic agent that raised a major controversy over its cardiovascular adverse effects. There is in vivo evidence that Rosiglitazone promotes cardiac hypertrophy by PPAR -γ-independent mechanisms. However, whether Rosiglitazone directly alters hypertrophic growth in cardiac cells is unknown. Chromatin remodeling by histone post-translational modifications has emerged as critical for many cardiomyopathies. Based on these observations, this study was initiated to investigate the cardiac hypertrophic effect of Rosiglitazone in a cellular model of primary neonatal rat cardiomyocytes (NRCM)...
August 16, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28822766/pseudomonas-aeruginosa-increases-muc1-expression-in-macrophages-through-the-tlr4-p38-pathway
#5
Kosuke Kato, Alec D Hanss, Marina A Zemskova, Nicole E Morgan, Marianne Kim, Kenneth S Knox, Yong Lin, Erik P Lillehoj, Kwang Chul Kim
Alveolar macrophages (AMs) play a critical role in the clearance of Pseudomonas aeruginosa (Pa) from the airways. However, hyper-activation of macrophages can impair bacterial clearance and contribute to morbidity and mortality. MUC1 mucin is a membrane-tethered, high molecular mass glycoprotein expressed on the apical surface of mucosal epithelial cells and some hematopoietic cells, including macrophages, where it counter-regulates inflammation. We recently reported that Pa up-regulates the expression of MUC1 in primary human AMs and THP-1 macrophages, and that increased MUC1 expression in these cells prevents hyper-activation of macrophages that appears to be important for host defense against severe pathology of Pa lung infection...
August 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28822725/berberine-modulates-amyloid-%C3%AE-peptide-generation-by-activating-amp-activated-protein-kinase
#6
Haijing Zhang, Chunhui Zhao, Guoqiong Cao, Limin Guo, Shuai Zhang, Yuexia Liang, Chunxia Qin, Ping Su, Hang Li, Wensheng Zhang
Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by memory deficits and cognitive decline. Excessive amyloid-β (Aβ) peptide aggregates and forms soluble oligomers and insoluble cerebral amyloid plaques, which is widely thought to be the underlying pathogenic mechanism of AD. Therefore, effective regulation of Aβ metabolism is an important aspect of preventing and improving AD. Berberine, which is the main active component of the traditional medicinal herb Coptidis rhizoma, has a positive effect on reducing Aβ levels...
August 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28822161/-synergistic-mechanism-of-traditional-chinese-medicine-based-on-target-combination-of-pept1-and-ppar%C3%AE
#7
Lian-Sheng Qiao, Yan-Kun Chen, Gang-Gang Luo, Fang Lu, Si-Jia Liu, Gong-Yu Li, Yan-Ling Zhang
Synergistic effect is main pharmacological mechanism of traditional Chinese medicine(TCM). The research method based on the key targets combination is an important method to explore the synergistic effect of TCM. Peptide transporter 1 (PepT1) is an essential target for drug uptake into the bloodstream, accounting for about 50% of the total transporter protein content from the small intestine. Peroxisome proliferator-activated receptor α(PPARα) is the lipid-lowering target of fibrates, which have a good hypolipidemic effect by activating PPARα...
June 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28822126/dimethyl-labeling-based-quantification-of-the-lysine-acetylome-and-proteome-of-plants
#8
Ines Lassowskat, Markus Hartl, Fabian Hosp, Paul J Boersema, Matthias Mann, Iris Finkemeier
Photorespiratory enzymes in different cellular compartments have been reported to be posttranslational modified by phosphorylation, disulfide formation, S-nitrosylation, glutathionylation, and lysine acetylation. However, not much is known yet about the function of these modifications to regulate the activities, localizations, or interactions of the proteins in this metabolic pathway. Hence, it will be of great importance to study these modifications and their temporal and conditional occurrence in more detail...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28822027/impact-of-orientation-and-flexibility-of-peptide-linkers-on-t-maritima-lipase-tm1350-displayed-on-bacillus-subtilis-spores-surface-using-cotb-as-fusion-partner
#9
Jawad Ullah, Huayou Chen, Ake Vastermark, Jinru Jia, Bangguo Wu, Zhong Ni, Yilin Le, Hongcheng Wang
Fusion protein construction often requires peptide linkers for prolonged conformation, extended stability and enzyme activity. In this study a series of fusion between Thermotoga maritima lipase Tm1350 and Bacillus subtillis coat protein CotB, comprising of several peptide linkers, with different length, flexibility and orientations were constructed. Effects of temperature, pH and chemicals were examined, on the activity of displayed enzyme. The fusion protein with longer flexible linkers L9 [(GGGGS)4] and L7 (GGGGS-GGGGS-EAAAK-EAAAK-GGGGS-GGGGS) possess 1...
August 18, 2017: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28821738/directly-monitor-protein-rearrangement-on-a-nanosecond-to-millisecond-time-scale
#10
Eric H-L Chen, Tony T-Y Lu, Jack C-C Hsu, Yufeng Jane Tseng, T-S Lim, Rita P-Y Chen
In order to directly observe the refolding kinetics from a partially misfolded state to a native state in the bottom of the protein-folding funnel, we used a "caging" strategy to trap the β-sheet structure of ubiquitin in a misfolded conformation. We used molecular dynamics simulation to generate the cage-induced, misfolded structure and compared the structure of the misfolded ubiquitin with native ubiquitin. Using laser flash irradiation, the cage can be cleaved from the misfolded structure within one nanosecond, and we monitored the refolding kinetics of ubiquitin from this misfolded state to the native state by photoacoustic calorimetry and photothermal beam deflection techniques on nanosecond to millisecond timescales...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821720/structural-basis-for-the-broad-substrate-specificity-of-the-human-tyrosylprotein-sulfotransferase-1
#11
Shinnosuke Tanaka, Toshiaki Nishiyori, Hidetaka Kojo, Reo Otsubo, Moe Tsuruta, Katsuhisa Kurogi, Ming-Cheh Liu, Masahito Suiko, Yoichi Sakakibara, Yoshimitsu Kakuta
Tyrosylprotein sulfotransferases (TPSTs) are enzymes that catalyze post-translational tyrosine sulfation of proteins. In humans, there are only two TPST isoforms, designated TPST1 and TPST2. In a previous study, we reported the crystal structure of TPST2, which revealed the catalytic mechanism of the tyrosine sulfation reaction. However, detailed molecular mechanisms underlying how TPSTs catalyse a variety of substrate proteins with different efficiencies and how TPSTs catalyze the sulfation of multiple tyrosine residues in a substrate protein remain unresolved...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821679/upf1-governs-synaptic-plasticity-through-association-with-a-stau2-rna-granule
#12
Tyson E Graber, Erika Freemantle, Mina Anadolu, Sarah Hébert-Seropian, Robyn MacAdam, Unkyung Shin, Huy-Dung Hoang, Tommy Alain, Jean-Claude Lacaille, Wayne S Sossin
Neuronal mRNAs can be packaged in reversibly stalled polysome granules prior to their transport to distant synaptic locales. Stimulation of synaptic metabotropic glutamate receptors (mGluRs) reactivates translation of these particular mRNAs to produce plasticity-related protein; a phenomenon exhibited during mGluR-mediated long-term depression (mGluR-LTD). This form of plasticity is deregulated in Fragile X Syndrome, a monogenic form of autism in humans, and understanding the stalling and reactivation mechanism could reveal new approaches to therapies...
August 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821663/agrp-neurons-can-increase-food-intake-during-conditions-of-appetite-suppression-and-inhibit-anorexigenic-parabrachial-neurons
#13
Rachel A Essner, Alison G Smith, Adam A Jamnik, Anna R Ryba, Zoe D Trutner, Matthew E Carter
To maintain energy homeostasis, orexigenic (appetite-inducing) and anorexigenic (appetite suppressing) brain systems functionally interact to regulate food intake. Within the hypothalamus, neurons that express agouti-related protein (AgRP) sense orexigenic factors and orchestrate an increase in food-seeking behavior. In contrast, calcitonin gene-related peptide (CGRP)-expressing neurons in the parabrachial nucleus (PBN) suppress feeding. PBN CGRP neurons become active in response to anorexigenic hormones released following a meal, including amylin, secreted by the pancreas, and cholecystokinin (CCK), secreted by the small intestine...
August 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821638/fluorescent-probes-for-selective-protein-labeling-in-lysosomes-a-case-of-%C3%AE-galactosidase-a
#14
Cornelius Bohl, Adam Pomorski, Susanne Seemann, Anne-Marie Knospe, Chaonan Zheng, Artur Krężel, Arndt Rolfs, Jan Lukas
Fluorescence-based live-cell imaging (LCI) of lysosomal glycosidases is often hampered by unfavorable pH and redox conditions that reduce fluorescence output. Moreover, most lysosomal glycosidases are low-mass soluble proteins that do not allow for bulky fluorescent protein fusions. We selected α-galactosidase A (GALA) as a model lysosomal glycosidase involved in Anderson-Fabry disease (AFD) for the current LCI approach. Examination of the subcellular localization of AFD-causing mutants can reveal the mechanism underlying cellular trafficking deficits...
August 15, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28821615/distinct-structural-mechanisms-determine-substrate-affinity-and-kinase-activity-of-protein-kinase-c%C3%AE
#15
Sangbae Lee, Titu Devamani, Hyun Deok Song, Manbir Sandhu, Adrien Larsen, Ruth Sommese, Abhinandan Jain, Nagarajan Vaidehi, Sivaraj Sivaramakrishnan
Protein kinase Cα (PKCα) belongs to the family of AGC kinases that phosphorylate multiple peptide substrates. While the consensus sequence motif has been identified and used to explain substrate specificity for PKCα, it does not inform the structural basis of substrate binding and kinase activity for diverse substrates phosphorylated by this kinase. The transient, dynamic, and unstructured nature of this protein-protein interaction has limited structural mapping of kinase-substrate interfaces. Here, using multiscale MD simulation-based predictions and FRET sensor-based experiments, we investigated the conformational dynamics of the kinase-substrate interface...
August 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821608/the-transmembrane-domain-of-the-p75-neurotrophin-receptor-stimulates-phosphorylation-of-the-trkb-tyrosine-kinase-receptor
#16
Khalil Saadipour, Michael MacLean, Sean Pirkle, Solav Ali, Maria Luisa Lopez-Redondo, David L Stokes, Moses V Chao
The function of protein products generated from intramembraneous cleavage by the γ-secretase complex is not well defined. The γ-secretase complex is responsible for the cleavage of several transmembrane proteins, most notably the amyloid precursor protein which results in Aβ, a transmembrane (TM) peptide. Another protein that undergoes a very similar γ-secretase cleavage is the p75 neurotrophin receptor. However, the fate of the cleaved p75 TM domain is unknown. p75 neurotrophin receptor is highly expressed during early neuronal development and regulates survival and process formation of neurons...
August 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821603/a-simple-light-isotope-metabolic-labeling-slim-labeling-strategy-a-powerful-tool-to-address-the-dynamics-of-proteome-variations-in-vivo
#17
Thibaut Léger, Camille Garcia, Laetitia Collomb, Jean-Michel Camadro
Many quantitative proteomics strategies rely on in vivo metabolic incorporation of amino acids with modified stable isotope profiles into proteins. These methods give rise to multiple ions for each peptide, with possible distortion of the isotopolog distribution, making the overall analytical process complex. We validated an alternative strategy, simple light isotope metabolic labeling (SLIM-labeling), which alleviates many of these problems. SLIM-labeling is based on the in vivo reduction of the isotopic composition of proteins using metabolic precursors with a unique light isotope composition to label all amino acids...
August 18, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28821582/identification-of-%C3%AE-enolase-as-a-prognostic-and-diagnostic-precancer-biomarker-in-oral-submucous-fibrosis
#18
Swarnendu Bag, Debabrata Dutta, Amrita Chaudhary, Bidhan Chandra Sing, Mousumi Pal, Ajoy Kumar Ray, Rita Banerjee, Ranjan Rashmi Paul, Amit Basak, Amit Kumar Das, Jyotirmoy Chatterjee
AIMS: Diagnostic ambiguities regarding the malignant potentiality of oral submucous fibrosis (OSF), an oral precancerous condition having dysplastic and non-dysplastic isoforms are the major failure for early intervention of oral squamous cell carcinoma (OSCC) patients. Our goal is to identify proteomic signatures from biopsies that can be used as precancer diagnostic marker for patient suffering from OSF. METHODS: The high throughput techniques adopting de novo peptide sequencing (1D SDS-PAGE coupled nanoLC MALDI tandem mass spectrometry (MS/MS)-based peptide mass fingerprint), immunohistochemistry (IHC), Western blot (WB) and real-time PCR (RT-PCR) analysis are considered for such biomarker identification and multilevel validations...
August 18, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28821462/ferritin-nanocage-with-intrinsically-disordered-proteins-and-affibody-a-platform-for-tumor-targeting-with-extended-pharmacokinetics
#19
Na Kyeong Lee, Eun Jung Lee, Soyoun Kim, Gi-Hoon Nam, Minwoo Kih, Yeonsun Hong, Cherlhyun Jeong, Yoosoo Yang, Youngro Byun, In-San Kim
Ferritin nanocages are of particular interest as a novel platform for drug and vaccine delivery, diagnosis, biomineralization scaffold and more, due to their perfect and complex symmetry, ideal physical properties, high biocompatibility, low toxicity profiles as well as easy manipulation by genetic or chemical strategies. However, a short half-life is still a hurdle for the translation of ferritin-based nanomedicines into the clinic. Here, we developed a series of rationally designed long circulating ferritin nanocages (LCFNs) with 'Intrinsically Disordered Proteins (IDP)' as a stealth layer for extending the half-life of ferritin nanocages...
August 15, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28821400/alzheimer-s-disease-as-oligomeropathy
#20
REVIEW
Kenjiro Ono
Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder and is characterized by pathological aggregates of amyloid β-protein (Aβ) and tau protein. On the basis of genetic evidence, biochemical data, and animal models, Aβ has been suggested to be responsible for the pathogenesis of AD (the amyloid hypothesis). Aβ molecules tend to aggregate to form oligomers, protofibrils, and mature fibrils. Although mature fibrils in the final stage have been thought to be the cause of AD pathogenesis, recent studies using synthetic Aβ peptides, a cell culture model, Aβ precursor protein transgenic mice models, and human samples, such as cerebrospinal fluids and postmortem brains of AD patients, suggest that pre-fibrillar forms (oligomers of Aβ) are more deleterious than are extracellular fibril forms...
August 16, 2017: Neurochemistry International
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