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Unfolded Proteins

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https://www.readbyqxmd.com/read/28634213/omega-3-fatty-acids-increase-the-unfolded-protein-response-and-improve-amyloid-%C3%AE-phagocytosis-by-macrophages-of-patients-with-mild-cognitive-impairment
#1
Henry M Olivera-Perez, Larry Lam, Johnny Dang, Weilan Jiang, Fabian Rodriguez, Elizabeth Rigali, Sarah Weitzman, Verna Porter, Liudmilla Rubi, Marco Morselli, Matteo Pellegrini, Milan Fiala
Mϕs of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-β1-42 (Aβ) phagocytosis and have low resistance to apoptosis by Aβ. ω-3 in vitro and in vivo and the ω-3 mediator, resolvin D1, in vitro increase Aβ phagocytosis by Mϕs of patients with MCI. We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Mϕs in a longitudinal study of fish-derived, ω-3-supplemented patients with MCI. Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1...
June 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28633842/effects-of-multi-frequency-ultrasound-pretreatment-under-low-power-density-on-the-enzymolysis-and-the-structure-characterization-of-defatted-wheat-germ-protein
#2
Xue Yang, Yunliang Li, Suyun Li, Ayobami Olayemi Oladejo, Yucheng Wang, Shanfen Huang, Cunshan Zhou, Yang Wang, Li Mao, Yanyan Zhang, Haile Ma, Xiaofei Ye
The effects of ultrasonic frequency mode, power density, pretreatment time and other parameters under low power density on the degree of hydrolysis (DH) of defatted wheat germ protein (DWGP) and angiotensin-I-converting enzyme (ACE) inhibitory activity of DWGP hydrolysate were studied in this research. Ultraviolet-visible (UV-Vis) spectra, free sulfhydryl (SH), disulfide bond (SS), surface hydrophobicity and hydrophobic protein content of ultrasound-pretreated protein and hydrophobic amino acid (HAA) content of alcalase-hydrolysate of DWGP were measured under optimized ultrasonic condition...
September 2017: Ultrasonics Sonochemistry
https://www.readbyqxmd.com/read/28633819/effects-of-ultrasound-pretreatment-with-different-frequencies-and-working-modes-on-the-enzymolysis-and-the-structure-characterization-of-rice-protein
#3
Xue Yang, Yunliang Li, Suyun Li, Ayobami Olayemi Oladejo, Siyu Ruan, Yucheng Wang, Shanfen Huang, Haile Ma
The effects of ultrasound pretreatment with different frequencies and working modes, including mono-frequency ultrasound (MFU), dual-frequency ultrasound (DFU) and tri-frequency ultrasound (TFU), on the degree of hydrolysis (DH) of rice protein (RP) and angiotensin-I-converting enzyme (ACE) inhibitory activity of RP hydrolysate were investigated. Ultraviolet-visible (UV) spectroscopy, fourier transform infrared (FTIR) spectroscopy, surface hydrophobicity and scanning electron microscopy (SEM) of RP pretreated with ultrasound were measured...
September 2017: Ultrasonics Sonochemistry
https://www.readbyqxmd.com/read/28633569/thermal-and-chemical-denaturation-of-colocasia-esculenta-tuber-agglutinin-from-%C3%AE-2%C3%AE-2-to-unfolded-state
#4
Himadri Biswas, Rajagopal Chattopadhyaya
The major tuber storage protein of Colocasia esculenta, is a monocot mannose-binding, widely used dietary lectin, containing two polypeptides of 12.0 and 12.4 kDa. By both gel filtration and dynamic light scattering at pH 7.2, the lectin has a α2β2 form of apparent molecular mass of 48.2 kDa and a hydrodynamic radius of 6.1±0.2 nm; however, at pH 3, it migrates as αβ and has a reduced hydrodynamic radius of 4.6±0.3 nm. Our circular dichroism spectroscopy studies show that the lectin retains approximately 100% of its secondary structure between pH 2-8, going down to ~90% for extreme acidic / alkaline conditions...
June 20, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28633019/edem-function-in-erad-protects-against-chronic-er-proteinopathy-and-age-related-physiological-decline-in-drosophila
#5
Michiko Sekiya, Akiko Maruko-Otake, Stephen Hearn, Yasufumi Sakakibara, Naoki Fujisaki, Emiko Suzuki, Kanae Ando, Koichi M Iijima
The unfolded protein response (UPR), which protects cells against accumulation of misfolded proteins in the ER, is induced in several age-associated degenerative diseases. However, sustained UPR activation has negative effects on cellular functions and may worsen disease symptoms. It remains unknown whether and how UPR components can be utilized to counteract chronic ER proteinopathies. We found that promotion of ER-associated degradation (ERAD) through upregulation of ERAD-enhancing α-mannosidase-like proteins (EDEMs) protected against chronic ER proteinopathy without inducing toxicity in a Drosophila model...
June 19, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28631090/subclinical-cutaneous-inflammation-remained-after-permeability-barrier-disruption-enhances-uv-sensitivity-by-altering-er-stress-responses-and-topical-pseudoceramide-prevents-them
#6
Sang Eun Lee, Yutaka Takagi, Takahiro Nishizaka, Ji Hwoon Baek, Han Jo Kim, Seung Hun Lee
Stratum corneum forms the UV barrier. The effect of ultraviolet B (UVB) on normal skin was extensively studied; however, its effect on barrier perturbed skin remains undefined. Both barrier perturbation and UVB irradiation induce endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in keratinocytes. Mild ER stress activates homeostatic UPR, while severe ER stress leads to abnormal UPR, promoting apoptosis and inflammation. Here, we investigated UV sensitivity and UVB-induced UPR in barrier-disrupted human skin and the effects of pseudoceramide-dominant emollient on UVB-induced skin responses...
June 19, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28630146/er-stress-causes-widespread-protein-aggregation-and-prion-formation
#7
Norfadilah Hamdan, Paraskevi Kritsiligkou, Chris M Grant
Disturbances in endoplasmic reticulum (ER) homeostasis create a condition termed ER stress. This activates the unfolded protein response (UPR), which alters the expression of many genes involved in ER quality control. We show here that ER stress causes the aggregation of proteins, most of which are not ER or secretory pathway proteins. Proteomic analysis of the aggregated proteins revealed enrichment for intrinsically aggregation-prone proteins rather than proteins which are affected in a stress-specific manner...
June 19, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28629863/the-unfolding-mechanism-of-monomeric-mutant-sod1-by-simulated-force-spectroscopy
#8
Mona Habibi, Jörg Rottler, Steven S Plotkin
Mechanical unfolding of mutated apo, disulfide-reduced, monomeric superoxide dismutase 1 protein (SOD1) has been simulated via force spectroscopy techniques, using both an all-atom (AA), explicit solvent model and a coarse-grained heavy-atom Gō (HA-Gō) model. The HA-Gō model was implemented at two different pulling speeds for comparison. The most-common sequence of unfolding in the AA model agrees well with the most-common unfolding sequence of the HA-Gō model, when the same normalized pulling rate was used...
June 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28629619/slow-interconversion-in-a-heterogeneous-unfolded-state-ensemble-of-outer-membrane-phospholipase-a
#9
Georg Krainer, Pablo Gracia, Erik Frotscher, Andreas Hartmann, Philip Gröger, Sandro Keller, Michael Schlierf
Structural and dynamic investigations of unfolded proteins are important for understanding protein-folding mechanisms as well as the interactions of unfolded polypeptide chains with other cell components. In the case of outer-membrane proteins (OMPs), unfolded-state properties are of particular physiological relevance, because these proteins remain unfolded for extended periods of time during their biogenesis and rely on interactions with binding partners to support proper folding. Using a combination of ensemble and single-molecule spectroscopy, we have scrutinized the unfolded state of outer-membrane phospholipase A (OmpLA) to provide a detailed view of its structural dynamics on timescales from nanoseconds to milliseconds...
June 16, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28628644/targeting-multiple-pro-apoptotic-signaling-pathways-with-curcumin-in-prostate-cancer-cells
#10
Mariela Rivera, Yanilda Ramos, Madeline Rodríguez-Valentín, Sheila López-Acevedo, Luis A Cubano, Jin Zou, Qiang Zhang, Guangdi Wang, Nawal M Boukli
Curcumin, an extract from the turmeric rhizome (Curcuma longa), is known to exhibit anti-inflammatory, antioxidant, chemopreventive and antitumoral activities against aggressive and recurrent cancers. Accumulative data indicate that curcumin may induce cancer cell death. However, the detailed mechanism underlying its pro-apoptotic and anti-cancer effects remains to be elucidated. In the present study, we examined the signaling pathways triggered by curcumin, specifically, the exact molecular mechanisms of curcumin-induced apoptosis in highly metastatic human prostate cancer cells...
2017: PloS One
https://www.readbyqxmd.com/read/28628313/tunneling-kinetics-and-non-adiabatic-proton-coupled-electron-transfer-in-proteins-the-effect-of-electric-fields-and-anharmonic-donor-acceptor-interactions
#11
Bridget Salna, Abdelkrim Benabbas, Douglas Russo, Paul M Champion
A proper description of proton donor-acceptor (D-A) distance fluctuations is crucial for understanding tunneling in proton-coupled electron transport (PCET). The typical harmonic approximation for the D-A potential results in a Gaussian probability distribution, which does not appropriately reflect the electronic repulsion forces that increase the energetic cost of sampling shorter D-A distances. Because these shorter distances are the primary channel for thermally activated tunneling, the analysis of tunneling kinetics depends sensitively on the inherently anharmonic nature of the D-A interaction...
June 19, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28628309/dissecting-orthosteric-contacts-for-a-reverse-fragment-based-ligand-design
#12
Arun Chandramohan, Nikhil Kumar Tulsian, Ganesh Srinivasan Anand
Orthosteric sites on proteins are formed typically from non-contiguous interacting sites in three dimensional space where the composite binding interaction of a biological ligand is mediated by multiple synergistic interactions of its constituent functional groups. Through these multiple interactions, ligands stabilize both the ligand binding site and the protein fold. However, relative energetic contributions of the individual contacts in these protein-ligand interactions are difficult to resolve. Deconvolution of the contributions of these various functional groups in natural inhibitors/ligand would greatly aid in iterative fragment-based drug discovery (FBDD)...
June 19, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28628040/lipogenic-transcription-factor-chrebp-mediates-fructose-induced-metabolic-adaptations-to-prevent-hepatotoxicity
#13
Deqiang Q Zhang, Xin Tong, Kyle VanDommelen, Neil Gupta, Kenneth Stamper, Graham F Brady, Zhuoxian Meng, Jiandie D Lin, Liangyou Y Rui, M Bishr Omary, Lei Yin
Epidemiologic and animal studies implicate overconsumption of fructose in the development of nonalcoholic fatty liver disease, but the molecular mechanisms underlying fructose-induced chronic liver diseases remain largely unknown. Here, we have presented evidence supporting the essential function of the lipogenic transcription factor carbohydrate response element-binding protein (ChREBP) in mediating adaptive responses to fructose and protecting against fructose-induced hepatotoxicity. In WT mice, a high-fructose diet (HFrD) activated hepatic lipogenesis in a ChREBP-dependent manner; however, in Chrebp-KO mice, a HFrD induced steatohepatitis...
June 19, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28627175/pull-and-paste-of-single-transmembrane-proteins
#14
Tetiana Serdiuk, Stefania Anna Mari, Daniel J Müller
How complex cytoplasmic membrane proteins insert and fold into cellular membranes is not fully understood.  One problem is the lack of suitable approaches that allow investigating the process by which polypeptides insert and fold into membranes.  Here, we introduce a method to mechanically unfold and extract a single polytopic -helical membrane protein, the lactose permease (LacY), from a phospholipid membrane, transport the fully unfolded polypeptide to another membrane and insert and refold the polypeptide into the native structure...
June 19, 2017: Nano Letters
https://www.readbyqxmd.com/read/28627018/the-nucleotide-free-state-of-heterotrimeric-g-proteins-%C3%AE-subunit-adopts-a-highly-stable-conformation
#15
Sai Krishna Andhirka, Ravichandran Vignesh, Gopala Krishna Aradhyam
Deciphering the mechanism of activation of heterotrimeric G proteins by their cognate receptors continues to be an intriguing area of research. The recently solved crystal structure of the ternary complex captured the receptor-bound α-subunit in an open conformation, without bound nucleotide has improved our understanding of the activation process. Despite these advancements, the mechanism by which the receptor causes GDP release from the α-subunit remains elusive. To elucidate the mechanism of activation, we studied guanine nucleotide-induced structural stability of the α-subunit (in response to thermal/chaotrope-mediated stress)...
June 19, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28626835/disrupted-er-to-golgi-trafficking-underlies-anti-hiv-drugs-and-alcohol-induced-cellular-stress-and-hepatic-injury
#16
Hui Han, Yuxin He, Jay Hu, Rhema Lau, Harrison Lee, Cheng Ji
Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are involved in anti-human immunodeficiency virus (HIV) drugs and alcohol-induced liver disease in a significant number of patients infected with HIV. However, the precise mechanism by which the drugs and alcohol cause ER stress remains elusive. We found that ritonavir-boosted lopinavir (RL) activated two canonical UPR branches without activation of the third canonical activating transcription factor 6 (ATF6) branch in either HepG2 cells or primary mouse hepatocytes...
April 2017: Hepatol Commun
https://www.readbyqxmd.com/read/28625916/er-stress-disturbs-sr-er-mitochondria-ca-2-transfer-implications-in-duchenne-muscular-dystrophy
#17
Marion Pauly, Claire Angebault-Prouteau, Haikel Dridi, Cécile Notarnicola, Valérie Scheuermann, Alain Lacampagne, Stefan Matecki, Jérémy Fauconnier
Besides its role in calcium (Ca(2+)) homeostasis, the sarco-endoplamic reticulum (SR/ER) controls protein folding and is tethered to mitochondria.Under pathophysiological conditions the unfolded protein response (UPR) is associated with disturbance in SR/ER-mitochondria crosstalk. Here, we investigated whether ER stress altered SR/ER-mitochondria links, Ca(2+) handling and muscle damage in WT (Wild Type) and mdx mice, the murine model of Duchenne Muscular Dystrophy (DMD). In WT mice, the SR/ER-mitochondria links were decreased in isolated FDB muscle fibers after injection of ER stress activator tunicamycin (TM)...
June 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28625789/maltoporin-lamb-unfolds-%C3%AE-hairpins-along-mechanical-stress-dependent-unfolding-pathways
#18
Johannes Thoma, Noah Ritzmann, Dominik Wolf, Estefania Mulvihill, Sebastian Hiller, Daniel J Müller
Upon mechanical pulling at either terminal end, β barrel outer membrane proteins stepwise unfold β strands or β hairpins until entirely extracted from the membrane. This unique unfolding pathway has been described for β barrels comprising 8, 14, or 22 β strands. Here we mechanically unfold the 18-stranded β barrel outer membrane protein LamB from Escherichia coli. We find that its mechanical unfolding pathway is shaped by the stepwise unfolding of β hairpins. However, we also observe that β hairpins can unfold groupwise...
June 6, 2017: Structure
https://www.readbyqxmd.com/read/28624420/biophysical-characterization-and-thermal-stability-of-pneumococcal-histidine-triad-protein-d-phtd-in-the-presence-of-zinc-and-manganese
#19
Salvador F Ausar, Kavisha Jayasundara, Lamees Akawi, Cristopher Roque, Anthony Sheung, Jian Hu, Marina Kirkitadze, Nausheen Rahman
The Pneumococcal Histidine Triad Protein D (PhtD) is believed to play a central role in pneumococcal metal ion homeostasis and has been proposed as a promising vaccine candidate against pneumococcal disease. To investigate for potential stabilizers, a panel of physiologically relevant metals was screened using the thermal shift assay and it was found that only Zn(2+) and Mn(2+) were able to increase PhtD melting temperature. Differential Scanning Calorimetry (DSC) analysis revealed a sequential unfolding of PhtD and the presence of at least 3 independent folding domains that can be stabilized by Zn(2+) and Mn(2+)...
June 14, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28624419/thermo-optical-protein-characterization-for-straightforward-preformulation-development
#20
Randy Wanner, Dennis Breitsprecher, Stefan Duhr, Philipp Baaske, Gerhard Winter
The determination of protein unfolding and aggregation characteristics during preformulation is of major significance for the development of biopharmaceuticals. The aim of this study was to investigate the feasibility of a new immobilization- and label-free thermo-optical approach as an orthogonal method for material and time saving early formulation and drugability screenings. In the experimental setup used, changes in the intrinsic tryptophan fluorescence of the protein were measured during IR-laser induced heating of the samples...
June 14, 2017: Journal of Pharmaceutical Sciences
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