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https://www.readbyqxmd.com/read/28098450/the-serum-amyloid-p-component-sap-interactome-in-human-plasma-containing-physiological-calcium-levels
#1
Ebbe Toftgaard Poulsen, Kata Wolff Pedersen, Anna Maria Marzeda, Jan Johannes Enghild
The pentraxin serum amyloid p component (SAP) is secreted by the liver and found in plasma at a concentration of approximately 30 mg/L. SAP is a 25 kDa homo-pentamer known to bind both protein and non-protein ligands, all in a calcium-dependent manner. The function of SAP is unclear, but likely involves the humoral innate immune system spanning the complement system, inflammation, and coagulation. Also, SAP is known to binding to the generic structure of amyloid deposits and possibly to protect these against proteolysis...
January 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/28097232/vps34-regulates-myofibril-proteostasis-to-prevent-hypertrophic-cardiomyopathy
#2
Hirotaka Kimura, Satoshi Eguchi, Junko Sasaki, Keiji Kuba, Hiroki Nakanishi, Shunsuke Takasuga, Masakazu Yamazaki, Akiteru Goto, Hiroyuki Watanabe, Hiroshi Itoh, Yumiko Imai, Akira Suzuki, Noboru Mizushima, Takehiko Sasaki
Hypertrophic cardiomyopathy (HCM) is a common heart disease with a prevalence of 1 in 500 in the general population. Several mutations in genes encoding cardiac proteins have been found in HCM patients, but these changes do not predict occurrence or prognosis and the molecular mechanisms underlying HCM remain largely elusive. Here we show that cardiac expression of vacuolar protein sorting 34 (Vps34) is reduced in a subset of HCM patients. In a mouse model, muscle-specific loss of Vps34 led to HCM-like manifestations and sudden death...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28096973/a-fission-yeast-cell-based-system-for-multidrug-resistant-hiv-1-proteases
#3
Zsigmond Benko, Dong Liang, Ge Li, Robert T Elder, Anindya Sarkar, Jun Takayama, Arun K Ghosh, Richard Y Zhao
BACKGROUND: HIV-1 protease (PR) is an essential enzyme for viral production. Thus, PR inhibitors (PIs) are the most effective class of anti-HIV drugs. However, the main challenge to the successful use of PI drugs in patient treatment is the emergence of multidrug resistant PRs (mdrPRs). This study aimed to develop a fission yeast cell-based system for rapid testing of new PIs that combat mdrPRs. RESULTS: Three mdrPRs were isolated from HIV-infected patients that carried seven (M7PR), ten (M10PR) and eleven (M11PR) PR gene mutations, respectively...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28096335/myofibril-breakdown-during-atrophy-is-a-delayed-response-requiring-the-transcription-factor-pax4-and-desmin-depolymerization
#4
Alexandra Volodin, Idit Kosti, Alfred Lewis Goldberg, Shenhav Cohen
A hallmark of muscle atrophy is the excessive degradation of myofibrillar proteins primarily by the ubiquitin proteasome system. In mice, during the rapid muscle atrophy induced by fasting, the desmin cytoskeleton and the attached Z-band-bound thin filaments are degraded after ubiquitination by the ubiquitin ligase tripartite motif-containing protein 32 (Trim32). To study the order of events leading to myofibril destruction, we investigated the slower atrophy induced by denervation (disuse). We show that myofibril breakdown is a two-phase process involving the initial disassembly of desmin filaments by Trim32, which leads to the later myofibril breakdown by enzymes, whose expression is increased by the paired box 4 (PAX4) transcription factor...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28095327/proteomic-and-peptidomic-analysis-of-human-sweat-with-emphasis-on-proteolysis
#5
Yijing Yu, Ioannis Prassas, Carla M J Muytjens, Eleftherios P Diamandis
: Sweat is produced by eccrine and apocrine glands and represents a biological fluid with established roles in thermo-regulation and host infection defense. The composition of sweat is highly dynamic and alters significantly in various skin and other disorders. Therefore, in-depth profiling of sweat protein composition is expected to augment our understanding of the pathobiology of several skin diseases and may lead to the identification of useful sweat-based disease biomarkers. We here reported an in-depth analysis of the human sweat proteome and peptidome...
January 14, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28089517/hypoxia-induces-a-hif-1-dependent-transition-from-collective-to-amoeboid-dissemination-in-epithelial-cancer-cells
#6
Steffi Lehmann, Veronika Te Boekhorst, Julia Odenthal, Roberta Bianchi, Sjoerd van Helvert, Kristian Ikenberg, Olga Ilina, Szymon Stoma, Jael Xandry, Liying Jiang, Reidar Grenman, Markus Rudin, Peter Friedl
Cancer metastases arise from a multi-step process that requires metastasizing tumor cells to adapt to signaling input from varying tissue environments [1]. As an early metastatic event, cancer cell dissemination occurs through different migration programs, including multicellular, collective, and single-cell mesenchymal or amoeboid migration [2-4]. Migration modes can interconvert based on changes in cell adhesion, cytoskeletal mechanotransduction [5], and/or proteolysis [6], most likely under the control of transcriptional programs such as the epithelial-to-mesenchymal transition (EMT) [7, 8]...
January 11, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28089448/structural-basis-for-the-interaction-of-a-human-small-heat-shock-protein-with-the-14-3-3-universal-signaling-regulator
#7
Nikolai N Sluchanko, Steven Beelen, Alexandra A Kulikova, Stephen D Weeks, Alfred A Antson, Nikolai B Gusev, Sergei V Strelkov
By interacting with hundreds of protein partners, 14-3-3 proteins coordinate vital cellular processes. Phosphorylation of the small heat shock protein, HSPB6, within its intrinsically disordered N-terminal domain activates its interaction with 14-3-3, ultimately triggering smooth muscle relaxation. After analyzing the binding of an HSPB6-derived phosphopeptide to 14-3-3 using isothermal calorimetry and X-ray crystallography, we have determined the crystal structure of the complete assembly consisting of the 14-3-3 dimer and full-length HSPB6 dimer and further characterized this complex in solution using fluorescence spectroscopy, small-angle X-ray scattering, and limited proteolysis...
December 30, 2016: Structure
https://www.readbyqxmd.com/read/28088539/the-dna-damage-response-of-c-elegans-affected-by-gravity-sensing-and-radiosensitivity-during-the-shenzhou-8-spaceflight
#8
Ying Gao, Dan Xu, Lei Zhao, Yeqing Sun
Space radiation and microgravity are recognized as primary and inevitable risk factors for humans traveling in space, but the reports regarding their synergistic effects remain inconclusive and vary across studies due to differences in the environmental conditions and intrinsic biological sensitivity. Thus, we studied the synergistic effects on transcriptional changes in the global genome and DNA damage response (DDR) by using dys-1 mutant and ced-1 mutant of C. elegans, which respectively presented microgravity-insensitivity and radiosensitivity when exposure to spaceflight condition (SF) and space radiation (SR)...
January 7, 2017: Mutation Research
https://www.readbyqxmd.com/read/28088490/microwave-based-treatments-of-wheat-kernels-do-not-abolish-gluten-epitopes-implicated-in-celiac-disease
#9
Carmen Gianfrani, Gianfranco Mamone, Barbara la Gatta, Alessandra Camarca, Luigia Di Stasio, Francesco Maurano, Stefania Picascia, Vito Capozzi, Giuseppe Perna, Gianluca Picariello, Aldo Di Luccia
Microwave based treatment (MWT) of wet wheat kernels induced a striking reduction of gluten, up to <20 ppm as determined by R5-antibodybased ELISA, so that wheat could be labeled as gluten-free. In contrast, analysis of gluten peptides by G12 antibody-based ELISA, mass spectrometry-based proteomics and in vitro assay with T cells of celiac subjects, indicated no difference of antigenicity before and after MWT. SDS-PAGE analysis and Raman spectroscopy demonstrated that MWT simply induced conformational modifications, reducing alcohol solubility of gliadins and altering the access of R5-antibody to the gluten epitopes...
January 11, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28087488/cathepsin-k-targeted-sub-micron-particles-for-regenerative-repair-of-vascular-elastic-matrix
#10
Brenton Jennewine, Jonathan Fox, Anand Ramamurthi
: Abdominal Aortic Aneurysms (AAA) involve slow dilation and weakening of the aortic wall due to breakdown of structural matrix components, such as elastic fibers by chronically overexpressed matrix metalloproteinases (MMPs), primarily, MMPs-2 and -9. Auto-regenerative repair of disrupted elastic fibers by smooth muscle cells (SMCs) at the AAA site is intrinsically poor and together with chronic proteolysis prevents restoration of elastin homeostasis, necessary to enable AAA growth arrest or regression to a healthy state...
January 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28079354/effect-of-excess-iodine-intake-on-thyroid-on-human-health
#11
Eftychia G Koukkou, Nikolaos D Roupas, Kostas B Markou
INTRODUCTION: The recommended daily intake of iodide, is 150 μg for adolescents and adults, 175 μg for pregnancy and 200 μg for lactation. Thyroid gland is an effective collector of iodine. EVIDENCE ACQUISITION: The active iodine uptake along the basolateral membrane of thyroid cell is followed by its transport to the apical edge of the cell and then to the follicle lumen. TSH acts through cAMP and stimulates NIS gene expression and protein synthesis. The major proportion of iodine in the thyroid gland is bound to Thyroglobulin...
January 12, 2017: Minerva Medica
https://www.readbyqxmd.com/read/28078551/the-proteolysis-adaptor-nbla-binds-to-the-n-terminus-of-%C3%AE-phycocyanin-implications-for-the-mechanism-of-phycobilisome-degradation
#12
Amelia Y Nguyen, William P Bricker, Hao Zhang, Daniel A Weisz, Michael L Gross, Himadri B Pakrasi
Phycobilisome (PBS) complexes are massive light-harvesting apparati in cyanobacteria that capture and funnel light energy to the photosystem. PBS complexes are dynamically degraded during nutrient deprivation, which causes severe chlorosis, and resynthesized during nutrient repletion. PBS degradation occurs rapidly after nutrient step down, and is specifically triggered by non-bleaching protein A (NblA), a small proteolysis adaptor that facilitates interactions between a Clp chaperone and phycobiliproteins...
January 11, 2017: Photosynthesis Research
https://www.readbyqxmd.com/read/28078417/covalent-organic-framework-coated-magnetic-graphene-as-a-novel-support-for-trypsin-immobilization
#13
Heping Wang, Fenglong Jiao, Fangyuan Gao, Xinyuan Zhao, Yan Zhao, Yehua Shen, Yangjun Zhang, Xiaohong Qian
Deep and efficient proteolysis is the critical premise in mass spectrometry-based bottom-up proteomics. It is difficult for traditional in-solution digestion to meet the requirement unless prolonged digestion time and enhanced enzyme dosage are employed, which makes the whole workflow time-consuming and costly. The abovementioned problems could be effectively ameliorated by anchoring many proteases on solid supports. In this work, covalent organic framework-coated magnetic graphene (MG@TpPa-1) was designed and prepared as a novel enzyme carrier for the covalent immobilization of trypsin with a high degree of loading (up to 268 μg mg(-1))...
January 11, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28069922/mechanisms-of-nmda-receptor-and-voltage-gated-l-type-calcium-channel-dependent-hippocampal-ltp-critically-rely-on-proteolysis-that-is-mediated-by-distinct-metalloproteinases
#14
Grzegorz Wiera, Daria Nowak, Inge Van Hove, Piotr Dziegiel, Lieve Moons, Jerzy W Mozrzymas
: Long-term potentiation (LTP) is widely perceived as a memory substrate and in the hippocampal CA3-CA1 pathway, distinct forms of LTP depend on N-methyl-D-aspartate (NMDA) receptors (nmdaLTP) or L-type voltage-gated calcium channels (vdccLTP). Long-term potentiation is also known to be effectively regulated by extracellular proteolysis that is mediated by various enzymes. Herein, we investigated whether in mice hippocampal slices these distinct forms of LTP are specifically regulated by different metalloproteinases (MMPs)...
January 9, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28069919/calpain-mediated-proteolysis-of-talin-and-fak-regulates-adhesion-dynamics-necessary-for-axon-guidance
#15
Patrick C Kerstein, Kevin M Patel, Timothy M Gomez
: Guidance of axons to their proper synaptic target sites requires spatially and temporally precise modulation of biochemical signals within growth cones. Ionic calcium (Ca(2+)) is an essential signal for axon guidance that mediates opposing affects on growth cone motility. The diverse effects of Ca(2+) arise from the precise localization of Ca(2+) signals into microdomains containing specific Ca(2+) effectors. For example, differences in the mechanical and chemical composition of the underlying substrata elicit local Ca(2+) signals within growth cone filopodia that regulate axon guidance through activation of the protease calpain...
January 9, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28069810/sensitive-versatile-fluorogenic-transmembrane-peptide-substrates-for-rhomboid-intramembrane-proteases
#16
Anežka Tichá, Stancho Stanchev, Jan Škerle, Jakub Began, Marek Ingr, Kateř Ina Švehlová, Lucie Polovinkin, Martin Růžička, Lucie Bednárová, Romana Hadravová, Edita Poláchová, Petra Rampírová, Jana Březinová, Václav Kašička, Pavel Majer, Kvido Strisovsky
Rhomboid proteases are increasingly being explored as potential drug targets, but their potent and specific inhibitors are not available, and strategies for inhibitor development are hampered by the lack of widely usable and easily modifiable in vitro activity assays. Here we address this bottleneck and report on the development of new fluorogenic transmembrane peptide substrates, which are cleaved by several unrelated rhomboid proteases, can be used both in detergent micelles and in liposomes, and contain red-shifted fluorophores that are suitable for high-throughput screening of compound libraries...
January 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28069396/multi-level-evaluation-of-escherichia-coli-polyphosphate-related-mutants-using-global-transcriptomic-proteomic-and-phenomic-analyses
#17
Macarena Varas, Camilo Valdivieso, Cecilia Mauriaca, Javiera Ortíz-Severín, Alberto Paradela, Ignacio Poblete-Castro, Ricardo Cabrera, Francisco P Chávez
BACKGROUND: Polyphosphate (polyP) is a linear biopolymer found in all living cells. In bacteria, mutants lacking polyphosphate kinase 1 (PPK1), the enzyme responsible for synthesis of most polyP, have many structural and functional defects. However, little is known about the causes of these pleiotropic alterations. The link between ppk1 deletion and those numerous phenotypes observed can be the result of complex molecular interactions that can be elucidated via a systems biology approach...
January 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28069035/fbw7-regulates-apoptosis-in-activated-b-cell-like-diffuse-large-b-cell-lymphoma-by-targeting-stat3-for-ubiquitylation-and-degradation
#18
Su Yao, Fangping Xu, Yu Chen, Yan Ge, Fen Zhang, Huijie Huang, Li Li, Danyi Lin, Xinlan Luo, Jie Xu, Donglan Luo, Xiaolan Zhu, Yanhui Liu
BACKGROUND: The ubiquitin-ligase Fbw7 acts as a tumor suppressor, targeting lots of proto-oncogenes for proteolysis. However, the exact role of Fbw7 in diffuse large B-cell lymphoma (DLBCL) development remains unclear. METHODS: We evaluated Fbw7 expression in patient samples of DLBCL using immunohistochemical staining. The effect of Fbw7 overexpression on cell viability and apoptosis was investigated using activated B-cell (ABC) like DLBCL cell lines. The mechanism of Fbw7 activity in DLBCL was investigated using immunoprecipitation, ubiquitination, western blot and qualitative analyses...
January 10, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28068062/sequence-defined-backbone-modifications-regulate-antibacterial-activity-of-oligoteas
#19
Mintu Porel, Dana N Thornlow, Christine M Artim, Christopher A Alabi
In response to the urgent need for new antibiotic development strategies, antimicrobial peptides (AMPs) and other synthetic polymers are being actively investigated as promising alternatives to traditional antibiotics. Although most AMPs display lytic activity against several types of bacteria, they have poor toxicology profiles and are susceptible to proteolysis in vivo. While many synthetic variants have been created to mimic AMPs by tuning the hydrophobic to cationic ratio of the side-chain groups, few have decoupled the effects of charge from hydrophobicity in discrete systems, and none have investigated the effect of backbone hydrophobicity...
January 9, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28067841/lectin-digestibility-and-stability-of-elderberry-antioxidants-to-heat-treatment-in-vitro
#20
Pilar Jiménez, Patricia Cabrero, Damian Cordoba-Diaz, Manuel Cordoba-Diaz, Manuel Garrosa, Tomás Girbés
Elderberry contains healthy low molecular weight nutraceuticals and lectins which are sequence-related to the elderberry allergen Sam n1. Some of these lectins are type II ribosome-inactivating proteins. The sensitivity of native lectins present in elderberry fruits and bark to the proteolysis triggered by in vitro simulated gastric and duodenal fluids has been investigated. It was found that these lectins are refractory to proteolysis. Nonetheless, incubation for 5-10 min in a boiling water bath completely sensitized them to the hydrolytic enzymes in vitro...
January 6, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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