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Unfolded Proteins

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https://www.readbyqxmd.com/read/28225824/caloric-restriction-reduces-the-systemic-progression-of-mouse-aapoaii-amyloidosis
#1
Lin Li, Jinko Sawashita, Xin Ding, Mu Yang, Zhe Xu, Hiroki Miyahara, Masayuki Mori, Keiichi Higuchi
In mouse senile amyloidosis, apolipoprotein (Apo) A-II is deposited extracellularly in many organs in the form of amyloid fibrils (AApoAII). Reduction of caloric intake, known as caloric restriction (CR), slows the progress of senescence and age-related disorders in mice. In this study, we intravenously injected 1 μg of isolated AApoAII fibrils into R1.P1-Apoa2c mice to induce experimental amyloidosis and investigated the effects of CR for the next 16 weeks. In the CR group, AApoAII amyloid deposits in the liver, tongue, small intestine and skin were significantly reduced compared to those of the ad libitum feeding group...
2017: PloS One
https://www.readbyqxmd.com/read/28224610/structural-changes-in-cartilage-and-collagen-studied-by-high-temperature-raman-spectroscopy
#2
Mark Fields, Nicholas Spencer, Jayesh Dudhia, Paul F McMillan
Understanding the high temperature behavior of collagen and collagenous tissue is important for surgical procedures and biomaterials processing for the food, pharmaceutical and cosmetics industries. One primary event for proteins is thermal denaturation that involves unfolding the polypeptide chains while maintaining the primary structure intact. Collagen in the extracellular matrix of cartilage and other connective tissue is a hierarchical material containing bundles of triple-helical fibers associated with water and proteoglycan components...
February 22, 2017: Biopolymers
https://www.readbyqxmd.com/read/28223518/integrated-view-of-internal-friction-in-unfolded-proteins-from-single-molecule-fret-contact-quenching-theory-and-simulations
#3
Andrea Soranno, Andrea Holla, Fabian Dingfelder, Daniel Nettels, Dmitrii E Makarov, Benjamin Schuler
Internal friction is an important contribution to protein dynamics at all stages along the folding reaction. Even in unfolded and intrinsically disordered proteins, internal friction has a large influence, as demonstrated with several experimental techniques and in simulations. However, these methods probe different facets of internal friction and have been applied to disparate molecular systems, raising questions regarding the compatibility of the results. To obtain an integrated view, we apply here the combination of two complementary experimental techniques, simulations, and theory to the same system: unfolded protein L...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28223361/covalently-linked-hslu-hexamers-support-a-probabilistic-mechanism-that-links-atp-hydrolysis-to-protein-unfolding-and-translocation
#4
Vladimir Baytshtok, Jiejen Chen, Steven E Glynn, Andrew R Nager, Robert A Grant, Tania A Baker, Robert T Sauer
The HslUV proteolytic machine consists of HslV, a double-ring self-compartmentalized peptidase, and one or two AAA+ HslU ring hexamers that hydrolyze ATP to power the unfolding of protein substrates and their translocation into the proteolytic chamber of HslV. Here, we use genetic-tethering and disulfide-bonding strategies to construct HslU pseudohexamers containing mixtures of ATPase active and inactive subunits at defined positions in the hexameric ring. Genetic tethering impairs HslV binding and degradation, even for pseudohexamers with six active subunits, but disulfide-linked pseudohexamers do not have these defects, indicating that the peptide tether interferes with HslV interactions...
February 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28222747/ire1%C3%AE-xbp1-pathway-promotes-melanoma-progression-by-regulating-il-6-stat3-signaling
#5
Cheng Chen, Xuejun Zhang
BACKGROUND: The IRE1α-XBP1 pathway is the most conserved branch of the unfolded protein response pathways, which are activated during endoplasmic reticulum (ER) stress caused by the accumulation of unfolded/misfolded proteins in the ER lumen. The IRE1α-XBP1 pathway plays a critical role in various cancers. However, the role of this pathway in melanoma cell growth remains unclear. METHODS: Sixty-one pairs of melanoma specimens and corresponding normal tissues from patients were stained with XBP1...
February 21, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28222026/hypoxic-regulation-of-the-expression-of-genes-encoded-estrogen-related-proteins-in-u87-glioma-cells-eff-ect-of-ire1-inhibition
#6
Minchenko Do, Riabovol Oo, Ratushna Oo, Minchenko Oh
OBJECTIVE: The aim of the present study was to examine the effect of inhibition of endoplasmic reticulum stress signaling, mediated by IRE1 (inositol requiring enzyme 1), which is a central mediator of the unfolded protein response on the expression of genes encoded estrogen related proteins (NRIP1/RIP140, TRIM16/EBBP, ESRRA/NR3B1, FAM162A/E2IG5, PGRMC2/PMBP, and SLC39A6/LIV-1) and their hypoxic regulation in U87 glioma cells for evaluation of their possible significance in the control of glioma cells proliferation...
January 1, 2017: Endocrine Regulations
https://www.readbyqxmd.com/read/28221789/raman-spectroscopy-reveals-selective-interactions-of-cytochrome-c-with-cardiolipin-that-correlate-with-membrane-permeability
#7
Jay P Kitt, David A Bryce, Shelley D Minteer, Joel M Harris
Permeabilization of the outer mitochondrial membrane is an integral step in apoptosis. The resulting release of pro-apoptotic signaling proteins leads to cell destruction through activation of the cysteine-aspartic protease (caspase) cascade. However, the mechanism of outer mitochondrial membrane (OMM) permeabilization remains unclear. It was recently shown that cytochrome c can induce pore formation in cardiolipin-containing phospholipid membranes leading to large dextran and protein permeability. In this work, the interaction of cytochrome c with cardiolpin-containing phospholipid vesicles, serving as models of the OMM, is investigated to probe cytochrome c-induced permeability...
February 21, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28220896/mitochondrial-dysregulation-secondary-to-endoplasmic-reticulum-stress-in-autosomal-dominant-tubulointerstitial-kidney-disease-umod-adtkd-umod
#8
Elisabeth Kemter, Thomas Fröhlich, Georg J Arnold, Eckhard Wolf, Rüdiger Wanke
'Autosomal dominant tubulointerstitial kidney disease - UMOD' (ADTKD-UMOD) is caused by impaired maturation and secretion of mutant uromodulin (UMOD) in thick ascending limb of Henle loop (TAL) cells, resulting in endoplasmic reticulum (ER) stress and unfolded protein response (UPR). To gain insight into pathophysiology, we analysed proteome profiles of TAL-enriched outer renal medulla samples from ADTKD-UMOD and control mice by quantitative LC-MS/MS. In total, 212 differentially abundant proteins were identified...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28218973/expression-of-rabies-virus-glycoprotein-in-the-methylotrophic-yeast-pichia-pastoris
#9
Safa Ben Azoun, Meriem Ben Zakour, Soufien Sghaier, Héla Kallel
Rabies is a fatal disease that can be prevented by vaccination. Different approaches were investigated to develop novel human rabies vaccines with improved features compared to the current available vaccines, among them is the use of heterologous gene expression technology. Here, we describe the expression of the surface rabies virus glycoprotein (RABV-G), which is the major antigen responsible for the induction of protective immunity, in Pichia pastoris. Six transformants were selected according to their gene copy number as determined by real time qPCR...
January 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/28218841/the-mechanism-of-human-apohemoglobin-unfolding
#10
Premila P Samuel, William Christopher Ou, George N Phillips, John Steven Olson
Removal of heme from human hemoglobin (Hb) results in formation of an apoglobin heterodimer. Titration of this apo-dimer with GdnHCl leads to biphasic unfolding curves indicating two distinct steps. Initially the heme pocket unfolds and generates a dimeric intermediate in which ~50% of the original helicity is lost, but the α1β1 interface is still intact. At higher [GdnHCl], this intermediate dissociates into unfolded monomers. This structural interpretation was verified by comparing GdnHCl titrations for adult human hemoglobin A (HbA), recombinant fetal human hemoglobin (HbF), recombinant Hb crosslinked with a single glycine linker between the α chains (rHb0...
February 20, 2017: Biochemistry
https://www.readbyqxmd.com/read/28216262/efis-lecture-understanding-the-ctla-4-checkpoint-in-the-maintenance-of-immune-homeostasis
#11
REVIEW
Lucy S K Walker
The past 20 years have heralded fascinating developments in the field of CTLA-4 biology. The CTLA-4 protein is a critical negative regulator of T cell immunity and its absence provokes severe lymphoproliferative disease. In a surprising twist, the generation of mixed bone marrow chimeric mice revealed that CTLA-4 predominantly functions in a cell-extrinsic manner, suggesting that CTLA-4 expressed on one cell can modify the behaviour of another cell. This was followed by the demonstration that CTLA-4 is highly expressed in regulatory T cells and can contribute to their suppressive activity...
February 16, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28216041/structure-of-a-type-1-secretion-system-abc-transporter
#12
Jacob L W Morgan, Justin F Acheson, Jochen Zimmer
Type-1 secretion systems (T1SSs) represent a widespread mode of protein secretion across the cell envelope in Gram-negative bacteria. The T1SS is composed of an inner-membrane ABC transporter, a periplasmic membrane-fusion protein, and an outer-membrane porin. These three components assemble into a complex spanning both membranes and providing a conduit for the translocation of unfolded polypeptides. We show that ATP hydrolysis and assembly of the entire T1SS complex is necessary for protein secretion. Furthermore, we present a 3...
February 15, 2017: Structure
https://www.readbyqxmd.com/read/28216023/immunogenicity-of-structurally-perturbed-hen-egg-lysozyme-adsorbed-to-silicone-oil-microdroplets-in-wild-type-and-transgenic-mouse-models
#13
Carly Fleagle Chisholm, Kaitlin R Soucie, Jane S Song, Pamela Strauch, Raul M Torres, John F Carpenter, Jack A Ragheb, Theodore W Randolph
Silicone oil microdroplets may act as adjuvants, promoting unwanted immune responses against both foreign and self-proteins. Proteins often unfold upon adsorption to silicone oil microdroplets, but it is unclear how such unfolding might affect the immune response. In this study, we found that hen egg lysozyme (HEL) readily adsorbed to silicone oil microdroplets and perturbed the conformation of HEL. We compared the immune response to injections of HEL formulated in the presence and absence of silicone oil microdroplets in both wild-type mice and transgenic littermates that express a soluble form of HEL (sHEL), thus rendering them immunologically tolerant to this nominal self-antigen...
February 16, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28215897/effects-of-body-condition-monensin-and-essential-oils-on-ruminal-lipopolysaccharide-concentration-inflammatory-markers-and-endoplasmatic-reticulum-stress-of-transition-dairy-cows
#14
C Drong, S Bühler, J Frahm, L Hüther, U Meyer, D von Soosten, D K Gessner, K Eder, H Sauerwein, S Dänicke
Evidence exists that dairy cows experience inflammatory-like phenomena in the transition period. Rumen health and alterations in metabolic processes and gene networks in the liver as the central metabolic organ might be key factors for cows' health and productivity in early lactation. This study made use of an animal model to generate experimental groups with different manifestations of postpartal fat mobilization and ketogenesis. In total, 60 German Holstein cows were allocated 6 wk antepartum to 3 high-body condition score (BCS) groups (BCS 3...
February 16, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28215703/structure-and-function-of-vibrio-cholerae-accessory-cholera-enterotoxin-in-presence-of-gold-nanoparticles-dependence-on-morphology
#15
Tanaya Chatterjee, Barun K Chatterjee, Tultul Saha, Kazi Mirajul Hoque, Pinak Chakrabarti
BACKGROUND: Accessory cholera enterotoxin (Ace) is a classical enterotoxin produced by Vibrio cholerae, the causative agent for cholera. Considering the crucial role of Ace in pathogenesis of cholera, we explored the modulation of structure/function of Ace using gold nanoparticles (AuNPs) of different size and shape - spherical (AuNS10 and AuNS100, the number indicating the diameter in nm) and rod (AuNR10). METHODS: Biophysical techniques have been used to find out structural modulation of Ace by AuNPs...
February 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28213961/chrysin-induces-death-of-prostate-cancer-cells-by-inducing-ros-and-er-stress
#16
Soomin Ryu, Whasun Lim, Fuller W Bazer, Gwonhwa Song
Chrysin is a natural flavone found in numerous plant extracts, honey and propolis that has multiple biological activities including anti-cancer effects. Understanding of biological mechanisms mediated in response to chrysin in cancerous cells may provide novel insight into chemotherapeutic approaches with reduced side effects in cancers. In the present study, we investigated functional roles of chrysin in progression of prostate cancer cells using DU145 and PC-3 cell lines. The results showed that chrysin induced apoptosis of cells evidenced by DNA fragmentation and increasing the population of both DU145 and PC-3 cells in the sub-G1 phase of the cell cycle...
February 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28213141/thermostability-of-photosystem-i-trimers-and-monomers-from-the-cyanobacterium-thermosynechococcus-elongatus
#17
Vladimir V Shubin, Irina V Terekhova, Yulia V Bolychevtseva, Eithar El-Mohsnawy, Matthias Rögner, Werner Mäntele, Marta J Kopczak, Enela Džafić
The performance of solar energy conversion into alternative energy sources in artificial systems highly depends on the thermostability of photosystem I (PSI) complexes Terasaki et al. (2007), Iwuchukwu et al. (2010), Kothe et al. (2013) . To assess the thermostability of PSI complexes from the thermophilic cyanobacterium Thermosynechococcus elongatus heating induced perturbations on the level of secondary structure of the proteins were studied. Changes were monitored by Fourier transform infrared (FT-IR) spectra in the mid-IR region upon slow heating (1°C per minute) of samples in D2O phosphate buffer (pD 7...
February 6, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28211814/are-major-dementias-triggered-by-poor-blood-flow-to-the-brain-theoretical-considerations
#18
Jack C de la Torre
There is growing evidence that chronic brain hypoperfusion plays a central role in the development of Alzheimer's disease (AD) long before dyscognitive symptoms or amyloid-β accumulation in the brain appear. This commentary proposes that dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and Creutzfeldt-Jakob disease (CJD) may also develop from chronic brain hypoperfusion following a similar but not identical neurometabolic breakdown as AD. The argument to support this conclusion is that chronic brain hypoperfusion, which is found at the early stages of the three dementias reviewed here, will reduce oxygen delivery and lower oxidative phosphorylation promoting a steady decline in the synthesis of the cell energy fuel adenosine triphosphate (ATP)...
February 15, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28211532/structure-of-a-lov-protein-in-apo-state-and-implications-for-construction-of-lov-based-optical-tools
#19
Vladimir Arinkin, Joachim Granzin, Katrin Röllen, Ulrich Krauss, Karl-Erich Jaeger, Dieter Willbold, Renu Batra-Safferling
Unique features of Light-Oxygen-Voltage (LOV) proteins like relatively small size (~12-19 kDa), inherent modularity, highly-tunable photocycle and oxygen-independent fluorescence have lately been exploited for the generation of optical tools. Structures of LOV domains reported so far contain a flavin chromophore per protein molecule. Here we report two new findings on the short LOV protein W619_1-LOV from Pseudomonas putida. First, the apo-state crystal structure of W619_1-LOV at 2.5 Å resolution reveals conformational rearrangements in the secondary structure elements lining the chromophore pocket including elongation of the Fα helix, shortening of the Eα-Fα loop and partial unfolding of the Eα helix...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28210980/molecular-mechanisms-of-ire1%C3%AE-ask1-pathway-reactions-to-unfolded-protein-response-in-drn-neurons-of-post-traumatic-stress-disorder-rats
#20
Fanzhen Kong, Fang Han, Yanhao Xu, Yuxiu Shi
The goal of this study was to further elucidate the molecular mechanisms of post-traumatic stress disorder (PTSD) pathogenesis and to provide experimental evidence for new drug targets for effective PTSD treatment. Expression changes of IRE1α, ASK1, and other downstream molecules of the IRE1α-ASK1 endoplasmic reticulum stress (ERS) signaling pathway were investigated. JNK, P38, CHOP, Bcl-2, and Bax were analyzed at both protein and mRNA levels of dorsal raphe nucleus (DRN) neurons of PTSD rats. The rat PTSD model was established via the single-prolonged stress (SPS) method...
February 16, 2017: Journal of Molecular Neuroscience: MN
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