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Unfolded Proteins

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https://www.readbyqxmd.com/read/29345569/a-complex-scenario-and-underestimated-challenge-the-tumor-microenvironment-er-stress-and-cancer-treatment
#1
Oleg I Chen, Yaroslav P Bobak, Oleh V Stasyk, Leoni A Kunz-Schughart
The paradoxical role of ER stress in malignant diseases is only just being unraveled and remains incompletely understood. A particular challenge is the complex interplay between spaciotemporal and locoregional microenvironmental constraints in solid tumors and stress responses upon treatment; thus, the potential for new combinatorial therapeutic options to foster the coincidence of ER stress-related deadly events is likely to be underestimated. Without claiming this review to be complete, we present a comprehensive overview of the signaling mechanisms associated with the unfolded protein response (UPR) and the molecular link to cell survival and death mechanisms...
January 16, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29345424/a-fluorescence-based-sensor-assay-that-monitors-general-protein-aggregation-in-human-cells
#2
Marisa Pereira, Diogo Tomé, Ana S Domingues, Ana S Varanda, Cristiana Paulo, Manuel A S Santos, Ana R Soares
Protein conformational disorders are characterized by disruption of protein folding and toxic accumulation of protein aggregates. Here we describe a sensitive and simple method to follow and monitor general protein aggregation in human cells. Heat shock protein 27 (HSP27) is an oligomeric small heat shock protein that binds and keeps unfolded proteins in a folding competent state. This high specificity of HSP27 for aggregated proteins can be explored to monitor aggregation in living cells by fusing it to a fluorescent protein as Green Fluorescent Protein (GFP)...
January 18, 2018: Biotechnology Journal
https://www.readbyqxmd.com/read/29344948/glycation-of-ovalbumin-after-high-intensity-ultrasound-pretreatment-effects-on-conformation-igg-ige-binding-ability-and-antioxidant-activity
#3
Wenhua Yang, Zongcai Tu, Hui Wang, Lu Zhang, Qidong Song
BACKGROUND: Ovalbumin (OVA), a protein with excellent nutritional and processing properties, is the major allergen of hen egg white. Previous study showed that high-intensity ultrasound treatment increased the IgG and IgE binding abilities by unfolding the conformational structure of OVA. It may allow modifying the IgG and IgE binding of OVA by combining high-intensity ultrasound with other methods, such as glycation, a promising method for the improvement of protein properties. RESULTS: Glycation with mannose (M) after ultrasound pretreatment at 0-600 W significantly reduced the IgG and IgE binding abilities and dramatically enhanced the antioxidant activity of OVA-M conjugates, with the lowest values of IgG and IgE binding and highest values of antioxidant capacity observed at 600W...
January 18, 2018: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/29344086/correlation-of-structure-function-and-protein-dynamics-in-gh7-cellobiohydrolases-from-trichoderma-atroviride-t-reesei-and-t-harzianum
#4
Anna S Borisova, Elena V Eneyskaya, Suvamay Jana, Silke F Badino, Jeppe Kari, Antonella Amore, Magnus Karlsson, Henrik Hansson, Mats Sandgren, Michael E Himmel, Peter Westh, Christina M Payne, Anna A Kulminskaya, Jerry Ståhlberg
Background: The ascomycete fungus Trichoderma reesei is the predominant source of enzymes for industrial conversion of lignocellulose. Its glycoside hydrolase family 7 cellobiohydrolase (GH7 CBH) TreCel7A constitutes nearly half of the enzyme cocktail by weight and is the major workhorse in the cellulose hydrolysis process. The orthologs from Trichoderma atroviride (TatCel7A) and Trichoderma harzianum (ThaCel7A) show high sequence identity with TreCel7A, ~ 80%, and represent naturally evolved combinations of cellulose-binding tunnel-enclosing loop motifs, which have been suggested to influence intrinsic cellobiohydrolase properties, such as endo-initiation, processivity, and off-rate...
2018: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/29343704/phosphorylation-induced-cochaperone-unfolding-promotes-kinase-recruitment-and-client-class-specific-hsp90-phosphorylation
#5
Ashleigh B Bachman, Dimitra Keramisanou, Wanping Xu, Kristin Beebe, Michael A Moses, M V Vasantha Kumar, Geoffrey Gray, Radwan Ebna Noor, Arjan van der Vaart, Len Neckers, Ioannis Gelis
During the Hsp90-mediated chaperoning of protein kinases, the core components of the machinery, Hsp90 and the cochaperone Cdc37, recycle between different phosphorylation states that regulate progression of the chaperone cycle. We show that Cdc37 phosphorylation at Y298 results in partial unfolding of the C-terminal domain and the population of folding intermediates. Unfolding facilitates Hsp90 phosphorylation at Y197 by unmasking a phosphopeptide sequence, which serves as a docking site to recruit non-receptor tyrosine kinases to the chaperone complex via their SH2 domains...
January 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29343429/translational-control-of-human-acetyl-coa-carboxylase-1-mrna-is-mediated-by-an-internal-ribosome-entry-site-in-response-to-er-stress-serum-deprivation-or-hypoxia-mimetic-cocl2
#6
Fabrizio Damiano, Mariangela Testini, Romina Tocci, Gabriele V Gnoni, Luisa Siculella
Acetyl-CoA carboxylase 1 (ACC1) is a cytosolic enzyme catalyzing the rate limiting step in de novo fatty acid biosynthesis. There is mounting evidence showing that ACC1 is susceptible to dysregulation and that it is over-expressed in liver diseases associated with lipid accumulation and in several cancers. In the present study, ACC1 regulation at the translational level is reported. Using several experimental approaches, the presence of an internal ribosome entry site (IRES) has been established in the 5' untranslated region (5' UTR) of the ACC1 mRNA...
January 14, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29341923/purification-chitooligosaccharide-binding-properties-and-thermal-stability-of-cia24-a-new-pp2-like-phloem-exudate-lectin-from-ivy-gourd-coccinia-indica
#7
Kishore Babu Bobbili, Debparna Datta, Saradamoni Mondal, Sirilatha Polepalli, Michael Mormann, Musti J Swamy
PP2-like chitin binding phloem exudate lectins, abundant in the sieve tube of cucurbits, have been implicated to play key roles in wound sealing and antipathogenic responses of the plant. Here we report the affinity purification, macromolecular characterization and carbohydrate binding properties of a new chitooligosaccharide-specific lectin from the phloem exudate of ivy gourds (Coccinia indica). The protein, CIA24, has a subunit mass of 24 kDa. Partial sequence analysis indicated that CIA24 exhibits high homology with CIA17 and other Cucurbitaceae PP2 proteins whereas CD spectroscopic studies suggested that β-sheets constitute the predominant secondary structure...
January 13, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29341886/regulation-of-hsf1-protein-stabilization-an-updated-review
#8
REVIEW
Chao Huang, Jingjing Wu, Li Xu, Jili Wang, Zhuo Chen, Rongrong Yang
Heat shock factor 1 (HSF1) is a transcriptional factor that determines the efficiency of heat shock responses (HSRs) in the cell. Given its function has been extensively studied in recent years, HSF1 is considered a potential target for the treatment of disorders associated with protein aggregation. The activity of HSF1 is traditionally regulated at the transcriptional level in which the transactivation domain of HSF1 is modified by extensive array of pos-translational modifications, such as phosphorylation, sumoylation, and acetylation...
January 13, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29340775/global-versus-local-mechanisms-of-temperature-sensing-in-ion-channels
#9
REVIEW
Cristina Arrigoni, Daniel L Minor
Ion channels turn diverse types of inputs, ranging from neurotransmitters to physical forces, into electrical signals. Channel responses to ligands generally rely on binding to discrete sensor domains that are coupled to the portion of the channel responsible for ion permeation. By contrast, sensing physical cues such as voltage, pressure, and temperature arises from more varied mechanisms. Voltage is commonly sensed by a local, domain-based strategy, whereas the predominant paradigm for pressure sensing employs a global response in channel structure to membrane tension changes...
January 17, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29339381/cholecystokinin-is-involved-in-triglyceride-fatty-acid-uptake-by-rat-adipose-tissue
#10
Adrian Plaza, Beatriz Merino, Victoria Cano, Gema Domínguez, Javier Pérez-Castells, Maria S Fernandez-Alfonso, Coralie Sengenès, Julie A Chowen, Mariano Ruiz-Gayo
The incorporation of plasma triglyceride (TG) fatty acids to white adipose tissue (WAT) depends on lipoprotein lipase (LPL), which is regulated by angiopoietin-like protein-4 (ANGPTL-4), an unfolding molecular chaperone that converts active LPL dimers into inactive monomers. The production of ANGPTL-4 is promoted by fasting and repressed by feeding. We hypothesized that the postprandial hormone cholecystokinin (CCK) facilitates the storage of dietary TG fatty acids in WAT by regulating the activity of the LPL/ANGPTL-4 axis and that it does so by acting directly on CCK receptors in adipocytes...
January 16, 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/29339327/the-chaperonin-cct-promotes-the-formation-of-fibrillar-aggregates-of-%C3%AE-tubulin
#11
Luis Pouchucq, Pablo Lobos-Ruiz, Gisela Araya, José María Valpuesta, Octavio Monasterio
The type II chaperonin CCT is involved in the prevention of the pathogenesis of numerous human misfolding disorders, as it sequesters misfolded proteins, blocks their aggregation and helps them to achieve their native state. In addition, it has been reported that CCT can prevent the toxicity of non-client amyloidogenic proteins by the induction of non-toxic aggregates, leading to new insight in chaperonin function as an aggregate remodeling factor. Here we add experimental evidence to this alternative mechanism by which CCT actively promotes the formation of conformationally different aggregates of γ-tubulin, a non-amyloidogenic CCT client protein, which are mediated by specific CCT-γ-tubulin interactions...
January 12, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29339092/structural-and-biochemical-analyses-reveal-ubiquitin-c-terminal-hydrolase-l1-as-a-specific-client-of-the-peroxiredoxin-ii-chaperone
#12
Sang Pil Lee, Chan Mi Park, Kyung Seok Kim, Eunji Kim, Moonkyung Jeong, Ji-Young Shin, Chul-Ho Yun, Kanghwa Kim, P Boon Chock, Ho Zoon Chae
Peroxiredoxins (Prxs) play dual roles as both thiol-peroxidases and molecular chaperones. Peroxidase activity enables various intracellular functions, however, the physiological roles of Prxs as chaperones are not well established. To study the chaperoning function of Prx, we previously sought to identify heat-induced Prx-binding proteins as the clients of a Prx chaperone. By using His-tagged Prx I as a bait, we separated ubiquitin C-terminal hydrolase-L1 (UCH-L1) as a heat-induced Prx I binding protein from rat brain crude extracts...
January 12, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29338201/self-assembly-of-spider-silk-fusion-proteins-comprising-enzymatic-and-fluorescence-activity
#13
Martin Humenik, Madeleine Mohrand, Thomas Scheibel
The recombinant spider silk protein eADF4(C16) was genetically fused either with esterase 2 (EST2) or green fluorescent protein (GFP). The fusions EST-eADF4(C16) and GFP-eADF4(C16) were spectroscopically investigated and showed native structures of EST and GFP. The structural integrity was confirmed by the enzymatic activity of EST and the fluorescence of GFP. The spider silk moiety retained its intrinsically unstructured conformation in solution and the self-assembly into either nanofibrils or nanoparticles could be controlled by the concentration of phosphate...
January 16, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29338043/search-for-independent-%C3%AE-%C3%AE-4-subdomains-in-a-%C3%AE-%C3%AE-8-barrel-%C3%AE-glucosidase
#14
Vitor M Almeida, Maira A Frutuoso, Sandro R Marana
Proteins that fold as (β/α)8 barrels are thought to have evolved from half-barrels that underwent duplication and fusion events. The evidence is particularly clear for small barrels, which have almost identical halves. Additionally, computational calculations of the thermodynamic stability of these structures in the presence of denaturants have revealed that (β/α)8 barrels contain two subunits or domains corresponding to half-barrels. Hence, within (β/α)8 barrels, half-barrels are self-contained units...
2018: PloS One
https://www.readbyqxmd.com/read/29337245/hepatic-alcohol-dehydrogenase-deficiency-induces-pancreatic-injury-in-chronic-ethanol-feeding-model-of-deer-mice
#15
Samir M Amer, Kamlesh K Bhopale, Ramu D Kakumanu, Vsevolod L Popov, Bill A Rampy, Inas H El-Mehallawi, Magdy M Ashmawy, G A Shakeel Ansari, Bhupendra S Kaphalia
The single most common cause of chronic pancreatitis (CP, a serious inflammatory disease) is chronic alcohol abuse, which impairs hepatic alcohol dehydrogenase (ADH, a major ethanol oxidizing enzyme). Previously, we found ~5 fold greater fatty acid ethyl esters (FAEEs), and injury in the pancreas of hepatic ADH deficient (ADH-) vs. hepatic normal ADH (ADH+) deer mice fed 3.5g% ethanol via liquid diet daily for two months. Therefore, progression of ethanol-induced pancreatic injury was determined in ADH- deer mice fed ethanol for four months to delineate the mechanism and metabolic basis of alcoholic chronic pancreatitis (ACP)...
January 11, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29336449/ph-dependent-cooperativity-and-existence-of-a-dry-molten-globule-in-the-folding-of-a-miniprotein-bbl
#16
Zhi Yue, Jana Shen
Solution pH plays an important role in protein dynamics, stability, and folding; however, detailed mechanisms remain poorly understood. Here we use continuous constant pH molecular dynamics in explicit solvent with pH replica exchange to describe the pH profile of the folding cooperativity of a miniprotein BBL, which has drawn intense debate in the past. Our data reconciled the two opposing hypotheses (downhill vs. two-state) and uncovered a sparsely populated unfolding intermediate. As pH is lowered from 7 to 5, the folding barrier vanishes...
January 16, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29336441/a-high-pressure-study-of-calmodulin-ligand-interactions-using-small-angle-x-ray-and-elastic-incoherent-neutron-scattering
#17
Süleyman Cinar, Samy Al-Ayoubi, Christian Sternemann, Judith Peters, Roland Winter, Claus Czeslik
Calmodulin (CaM) is a Ca2+ sensor and mediates Ca2+ signaling through binding of numerous target ligands. The binding of ligands by Ca2+-saturated CaM (holo-CaM) is governed by attractive hydrophobic and electrostatic interactions that are weakened under high pressure in aqueous solutions. Moreover, the potential formation of void volumes upon ligand binding creates a further source of pressure sensitivity. Hence, high pressure is a suitable thermodynamic variable to probe protein-ligand interactions. In this study, we compare the binding of two different ligands to holo-CaM as a function of pressure by using X-ray and neutron scattering techniques...
January 16, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29335505/perk-mediated-translational-control-is-required-for-collagen-secretion-in-chondrocytes
#18
Satoshi Hisanaga, Masato Miyake, Shusuke Taniuchi, Miho Oyadomari, Masatoshi Morimoto, Ryosuke Sato, Jun Hirose, Hiroshi Mizuta, Seiichi Oyadomari
As chondrocytes are highly secretory and they experience a variety of stresses, physiological unfolded protein response (UPR) signalling is essential for extracellular matrix (ECM) secretion and chondrogenesis. In the three branches of the UPR pathway, PERK governs the translational attenuation and transcriptional upregulation of amino acid and redox metabolism and induction of apoptosis. It was previously demonstrated that a defect of the PERK branch of the UPR signalling pathway causes the accumulation of unfolded proteins, leading to cell death without perturbing endoplasmic reticulum (ER)-to-Golgi transport in pancreatic β cells...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29334736/hydration-behavior-along-the-folding-pathways-of-trpzip4-trpzip5-and-trpzip6
#19
Madhulika Gupta, Prabir Khatua, Charusita Chakravarty, Sanjoy Bandyopadhyay
The microscopic properties of water confined within different segments of Trpzip4 (TZ4), Trpzip5 (TZ5) and Trzpip6 (TZ6) have been compared for all the states characterized along their folding pathways. In particular, structural ordering, energetics, and dynamics of water have been examined as the peptide unfolds along the free energy landscape. It is observed that the structuring of tetrahedral network as well as translational and rotational motions of hydration waters confined within the strands and the turn regions are very different, revealing motional heterogeneity in small 16-residue trpzips...
January 15, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29332998/high-pressure-epr-spectroscopy-studies-of-the-e-coli-lipopolysaccharide-transport-proteins-lpta-and-lptc
#20
Kathryn M Schultz, Candice S Klug
The use of pressure is an advantageous approach to the study of protein structure and dynamics because it can shift the equilibrium populations of protein conformations toward higher energy states that are not of sufficient population to be observable at atmospheric pressure. Recently, the Hubbell group at the University of California, Los Angeles, reintroduced the application of high pressure to the study of proteins by electron paramagnetic resonance (EPR) spectroscopy. This methodology is possible using X-band EPR spectroscopy due to advances in pressure intensifiers, sample cells, and resonators...
December 2017: Applied Magnetic Resonance
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