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Unfolded Proteins

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https://www.readbyqxmd.com/read/28530745/self-assembling-peptide-and-protein-amyloids-from-structure-to-tailored-function-in-nanotechnology
#1
REVIEW
Gang Wei, Zhiqiang Su, Nicholas P Reynolds, Paolo Arosio, Ian W Hamley, Ehud Gazit, Raffaele Mezzenga
Self-assembled peptide and protein amyloid nanostructures have traditionally been considered only as pathological aggregates implicated in human neurodegenerative diseases. In more recent times, these nanostructures have found interesting applications as advanced materials in biomedicine, tissue engineering, renewable energy, environmental science, nanotechnology and material science, to name only a few fields. In all these applications, the final function depends on: (i) the specific mechanisms of protein aggregation, (ii) the hierarchical structure of the protein and peptide amyloids from the atomistic to mesoscopic length scales and (iii) the physical properties of the amyloids in the context of their surrounding environment (biological or artificial)...
May 22, 2017: Chemical Society Reviews
https://www.readbyqxmd.com/read/28530710/engineering-protein-stability-with-atomic-precision-in-a-monomeric-miniprotein
#2
Emily G Baker, Christopher Williams, Kieran L Hudson, Gail J Bartlett, Jack W Heal, Kathryn L Porter Goff, Richard B Sessions, Matthew P Crump, Derek N Woolfson
Miniproteins simplify the protein-folding problem, allowing the dissection of forces that stabilize protein structures. Here we describe PPα-Tyr, a designed peptide comprising an α-helix buttressed by a polyproline II helix. PPα-Tyr is water soluble and monomeric, and it unfolds cooperatively with a midpoint unfolding temperature (TM) of 39 °C. NMR structures of PPα-Tyr reveal proline residues docked between tyrosine side chains, as designed. The stability of PPα is sensitive to modifications in the aromatic residues: replacing tyrosine with phenylalanine, i...
May 22, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28530269/a-critical-comparison-of-coarse-grained-structure-based-approaches-and-atomic-models-of-protein-folding
#3
Jie Hu, Tao Chen, Moye Wang, Hue Sun Chan, Zhuqing Zhang
Structure-based coarse-grained Gō-like models have been used extensively in deciphering protein folding mechanisms because of their simplicity and tractability. Meanwhile, explicit-solvent molecular dynamics (MD) simulations with physics-based all-atom force fields have been applied successfully to simulate folding/unfolding transitions for several small, fast-folding proteins. To explore the degree to which coarse-grained Gō-like models and their extensions to incorporate nonnative interactions are capable of producing folding processes similar to those in all-atom MD simulations, here we systematically compare the computed unfolded states, transition states, and transition paths obtained using coarse-grained models and all-atom explicit-solvent MD simulations...
May 22, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28528361/toward-the-identification-and-the-targeting-of-key-players-of-the-mitochondrial-unfolded-protein-response-upr-mt-in-cancer
#4
EDITORIAL
Doris Germain
No abstract text is available yet for this article.
May 20, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/28528000/biophysical-insight-into-structure-function-relation-of-allium-sativum-protease-inhibitor-by-thermal-chemical-and-ph-induced-modulation-using-comprehensive-spectroscopic-analysis
#5
Tooba Naz Shamsi, Romana Parveen, Huma Naz, Md Anzarul Haque, Sadaf Fatima
In this study, we have analyzed the structural and functional changes in the nature of Allium sativum Protease Inhibitor (ASPI) on undergoing various denaturation with variable range of pH, temperature and urea (at pH 8.2). ASPI being anti-tryptic in nature has native molecular mass of ∼15kDa. The conformational stability, functional parameters and their correlation were estimated under different conditions using circular dichroism, fluorescence and activity measurements. ASPI was found to fall in belongs to α+β protein...
May 17, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28527593/a-structural-and-functional-study-of-gln147-deamidation-in-%C3%AE-a-crystallin-a-major-site-of-modification-in-human-cataract
#6
Nicholas J Ray, Damien Hall, John A Carver
Deamidation of Glu147 in human αA-crystallin is common in aged cataractous lenses (Hains and Truscott, Invest. Ophthalmol. Vis. Sci. 2010, 51, 3107). Accordingly, this modification may have a causative effect in cataract. αA-crystallin is a small heat-shock molecular chaperone protein that prevents aggregation of proteins and is the principal defence against crystallin protein unfolding and aggregation in the ageing lens. Deamidated Q147E αA-crystallin was structurally characterised using a variety of spectroscopic and biophysical methods, including NMR, circular dichroism and fluorescence spectroscopy and dynamic light scattering...
May 17, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28527571/progesterone-receptor-signaling-in-uterine-myometrial-physiology-and-preterm-birth
#7
San-Pin Wu, Francesco J DeMayo
Myometrium holds the structural integrity for the uterus and generates force for parturition with its primary component, the smooth muscle cells. The progesterone receptor mediates progesterone-dependent signaling and connects to a network of pathways for regulation of contractility and inflammatory responses in myometrium. Dysfunctional progesterone signaling has been linked to pregnancy complications including preterm birth. In the present review, we summarize recent findings on modifiers and effectors of the progesterone receptor signaling...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28526017/the-effect-of-hypoxia-on-the-lipidome-of-recombinant-pichia-pastoris
#8
Núria Adelantado, Pablo Tarazona, Karlheinz Grillitsch, Xavier García-Ortega, Sergi Monforte, Francisco Valero, Ivo Feussner, Günther Daum, Pau Ferrer
BACKGROUND: Cultivation of recombinant Pichia pastoris (Komagataella sp.) under hypoxic conditions has a strong positive effect on specific productivity when the glycolytic GAP promoter is used for recombinant protein expression, mainly due to upregulation of glycolytic conditions. In addition, transcriptomic analyses of hypoxic P. pastoris pointed out important regulation of lipid metabolism and unfolded protein response (UPR). Notably, UPR that plays a role in the regulation of lipid metabolism, amino acid metabolism and protein secretion, was found to be upregulated under hypoxia...
May 19, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28523846/a-novel-rapid-analysis-using-mass-spectrometry-to-evaluate-downstream-refolding-of-recombinant-human-insulin-like-growth-factor-1-mecasermin
#9
Kenichiro Furuki, Toshimasa Toyo'oka, Hideto Yamaguchi
RATIONALE: Mecasermin is used to treat elevated blood sugar as well as growth hormone-resistant Laron-type dwarfism. Mecasermin isolated from inclusion bodies in extracts of E.coli must be refolded to acquire sufficient activity. However, there is no rapid analytical method for monitoring refolding during the purification process. METHODS: We prepared mecasermin drug product, in-process samples during the oxidation of mecasermin, forced-reduced mecasermin, and aerially oxidized mecasermin after forced reduction...
May 19, 2017: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/28522876/comparative-proteomic-analysis-of-the-mitochondria-associated-er-membrane-mam-in-a-long-term-type-2-diabetic-rodent-model
#10
Jacey Hongjie Ma, Shichen Shen, Joshua J Wang, Zhanwen He, Amanda Poon, Jun Li, Jun Qu, Sarah X Zhang
The mitochondria-associated ER membrane (MAM) plays a critical role in cellular energetics and calcium homeostasis; however, how MAM is affected under diabetic condition remains elusive. This study presented a comprehensive proteome profiling of isolated brain MAM from long-term type 2 diabetic mice vs. non-diabetic controls. MAM protein was extracted efficiently by a surfactant-aided precipitation/on-pellet digestion (SOD) method, and MAM proteome was quantified by an ion-current-based MS1 method combined with nanoLC-MS/MS...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28522638/a-self-consistent-structural-perturbation-approach-for-determining-the-magnitude-and-extent-of-allosteric-coupling-in-proteins
#11
Nandakumar Rajasekaran, Athi N Naganathan
Elucidating the extent of energetic coupling between residues in single-domain proteins, a fundamental determinant of allostery, information transfer and folding cooperativity, has remained a grand challenge. While several sequence- and structure-based approaches have been proposed, a self-consistent description that is simultaneously compatible with unfolding thermodynamics is lacking. We had recently developed a simple structural perturbation protocol that captures the changes in thermodynamic stabilities induced by point mutations within the protein interior...
May 18, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28521011/translation-initiation-events-on-structured-eukaryotic-mrnas-generate-gene-expression-noise
#12
Estelle Dacheux, Naglis Malys, Xiang Meng, Vinoy Ramachandran, Pedro Mendes, John Eg McCarthy
Gene expression stochasticity plays a major role in biology, creating non-genetic cellular individuality and influencing multiple processes, including differentiation and stress responses. We have addressed the lack of knowledge about posttranscriptional contributions to noise by determining cell-to-cell variations in the abundance of mRNA and reporter protein in yeast. Two types of structural element, a stem-loop and a poly(G) motif, not only inhibit translation initiation when inserted into an mRNA 5΄ untranslated region, but also generate noise...
May 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28518150/cycloheximide-promotes-paraptosis-induced-by-inhibition-of-cyclophilins-in-glioblastoma-multiforme
#13
Lin Wang, Justin H Gundelach, Richard J Bram
Cancer is the second leading cause of death worldwide. Current treatment strategies based on multi-agent chemotherapy and/or radiation regimens have improved overall survival in some cases. However, resistance to apoptosis often develops in cancer cells, and its occurrence is thought to contribute to treatment failure. Non-apoptotic cell death mechanisms have become of great interest, therefore, in hopes that they would bypass tumor cell resistance. Glioblastoma multiforme (GBM), a grade IV astrocytic tumor is the most frequent brain tumor in adults, and has a high rate of mortality...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28516908/an-optimized-strategy-to-measure-protein-stability-highlights-differences-between-cold-and-hot-unfolded-states
#14
Caterina Alfano, Domenico Sanfelice, Stephen R Martin, Annalisa Pastore, Piero Andrea Temussi
Macromolecular crowding ought to stabilize folded forms of proteins, through an excluded volume effect. This explanation has been questioned and observed effects attributed to weak interactions with other cell components. Here we show conclusively that protein stability is affected by volume exclusion and that the effect is more pronounced when the crowder's size is closer to that of the protein under study. Accurate evaluation of the volume exclusion effect is made possible by the choice of yeast frataxin, a protein that undergoes cold denaturation above zero degrees, because the unfolded form at low temperature is more expanded than the corresponding one at high temperature...
May 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28516782/exploring-site-specific-n-glycosylation-of-hek293-and-plant-produced-human-iga-isotypes
#15
Kathrin Göritzer, Daniel Maresch, Friedrich Altmann, Christian Obinger, Richard Strasser
The full potential of recombinant Immunoglobulin A as therapeutic antibody is not fully explored, owing to the fact that structure-function relationships of these extensively glycosylated proteins are not well understood. Here, monomeric IgA1, IgA2m(1) and IgA2m(2) variants of the anti-HER2 antibody (IgG1) trastuzumab were expressed in glyco-engineered Nicotiana benthamiana plants and in human HEK293-6E cells. All three IgA isotypes were purified and subjected to biophysical and biochemical characterization...
May 18, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28515481/conserved-presence-of-g-quadruplex-forming-sequences-in-the-long-terminal-repeat-promoter-of-lentiviruses
#16
Rosalba Perrone, Enrico Lavezzo, Giorgio Palù, Sara N Richter
G-quadruplexes (G4s) are secondary structures of nucleic acids that epigenetically regulate cellular processes. In the human immunodeficiency lentivirus 1 (HIV-1), dynamic G4s are located in the unique viral LTR promoter. Folding of HIV-1 LTR G4s inhibits viral transcription; stabilization by G4 ligands intensifies this effect. Cellular proteins modulate viral transcription by inducing/unfolding LTR G4s. We here expanded our investigation on the presence of LTR G4s to all lentiviruses. G4s in the 5'-LTR U3 region were completely conserved in primate lentiviruses...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28512218/ubiquitin-and-atp-dependent-unfoldase-activity-of-p97-vcp%C3%A2-nploc4%C3%A2-ufd1l-is-enhanced-by-a-mutation-that-causes-multisystem-proteinopathy
#17
Emily E Blythe, Kristine C Olson, Vincent Chau, Raymond J Deshaies
p97 is a "segregase" that plays a key role in numerous ubiquitin (Ub)-dependent pathways such as ER-associated degradation. It has been hypothesized that p97 extracts proteins from membranes or macromolecular complexes to enable their proteasomal degradation; however, the complex nature of p97 substrates has made it difficult to directly observe the fundamental basis for this activity. To address this issue, we developed a soluble p97 substrate-Ub-GFP modified with K48-linked ubiquitin chains-for in vitro p97 activity assays...
May 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28509380/amyloid-is-essential-but-insufficient-for-alzheimer-causation-addition-of-subcellular-cofactors-is-required-for-dementia
#18
REVIEW
Jeffrey Fessel
OBJECTIVE: The aim of this study is to examine the hypotheses stating the importance of amyloid or of its oligomers in the pathogenesis of Alzheimer's disease (AD). METHODS: Published studies were examined. RESULTS: The importance of amyloid in the pathogenesis of AD is well established, yet accepting it as the main cause for AD is problematic, because amyloid-centric treatments have provided no clinical benefit and about one-third of cognitively normal, older persons have cerebral amyloid plaques...
May 16, 2017: International Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28507523/autism-spectrum-disorders-and-schizophrenia-spectrum-disorders-excitation-inhibition-imbalance-and-developmental-trajectories
#19
Roberto Canitano, Mauro Pallagrosi
Autism spectrum disorders (ASD) and schizophrenia spectrum disorders (SSD) share clinical and genetic components that have long been recognized. The two disorders co-occur more frequently than would be predicted by their respective prevalence, suggesting that a complex, multifactor association is involved. However, DSM-5 maintains the distinction between ASD, with core social and communication impairments, and SSD, including schizophrenia (SCZ), with hallucinations, delusions, and thought disorder as essential features...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28507517/the-role-of-unfolded-protein-response-and-mitogen-activated-protein-kinase-signaling-in-neurodegenerative-diseases-with-special-focus-on-prion-diseases
#20
REVIEW
Syed Zahid Ali Shah, Deming Zhao, Tariq Hussain, Lifeng Yang
Prion diseases are neurodegenerative pathologies characterized by the accumulation of a protease-resistant form of the cellular prion protein named prion protein scrapie (PrP(Sc)) in the brain. PrP(Sc) accumulation in the endoplasmic reticulum (ER) result in a dysregulated calcium (Ca(2+)) homeostasis and subsequent initiation of unfolded protein response (UPR) leading to neuronal dysfunction and apoptosis. The molecular mechanisms for the transition between adaptation to ER stress and ER stress-induced apoptosis are still unclear...
2017: Frontiers in Aging Neuroscience
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