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Chaperones

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https://www.readbyqxmd.com/read/28107649/rpa-interacts-with-hira-and-regulates-h3-3-deposition-at-gene-regulatory-elements-in-mammalian-cells
#1
Honglian Zhang, Haiyun Gan, Zhiquan Wang, Jeong-Heon Lee, Hui Zhou, Tamas Ordog, Marc S Wold, Mats Ljungman, Zhiguo Zhang
The histone chaperone HIRA is involved in depositing histone variant H3.3 into distinct genic regions, including promoters, enhancers, and gene bodies. However, how HIRA deposits H3.3 to these regions remains elusive. Through a short hairpin RNA (shRNA) screening, we identified single-stranded DNA binding protein replication protein A (RPA) as a regulator of the deposition of newly synthesized H3.3 into chromatin. We show that RPA physically interacts with HIRA to form RPA-HIRA-H3.3 complexes, and it co-localizes with HIRA and H3...
January 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28107647/programmed-ribosomal-frameshifting-generates-a-copper-transporter-and-a-copper-chaperone-from-the-same-gene
#2
Sezen Meydan, Dorota Klepacki, Subbulakshmi Karthikeyan, Tõnu Margus, Paul Thomas, John E Jones, Yousuf Khan, Joseph Briggs, Jonathan D Dinman, Nora Vázquez-Laslop, Alexander S Mankin
Metal efflux pumps maintain ion homeostasis in the cell. The functions of the transporters are often supported by chaperone proteins, which scavenge the metal ions from the cytoplasm. Although the copper ion transporter CopA has been known in Escherichia coli, no gene for its chaperone had been identified. We show that the CopA chaperone is expressed in E. coli from the same gene that encodes the transporter. Some ribosomes translating copA undergo programmed frameshifting, terminate translation in the -1 frame, and generate the 70 aa-long polypeptide CopA(Z), which helps cells survive toxic copper concentrations...
January 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28107645/a-cu-rious-ribosomal-profiling-pattern-leads-to-the-discovery-of-ribosomal-frameshifting-in-the-synthesis-of-a-copper-chaperone
#3
John F Atkins, Gary Loughran, Pavel V Baranov
In many bacteria, separate genes encode a copper binding chaperone and a copper efflux pump, but in some the chaperone encoding gene has been elusive. In this issue of Molecular Cell, Meydan et al. (2017) report that ribosomes translating the ORF that encodes the copper pump frequently frameshift and terminate to produce the copper chaperone.
January 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28107462/cytochrome-c-oxidase-biogenesis-and-metallochaperone-interactions-steps-in-the-assembly-pathway-of-a-bacterial-complex
#4
Sonja Schimo, Ilka Wittig, Klaas M Pos, Bernd Ludwig
Biogenesis of mitochondrial cytochrome c oxidase (COX) is a complex process involving the coordinate expression and assembly of numerous subunits (SU) of dual genetic origin. Moreover, several auxiliary factors are required to recruit and insert the redox-active metal compounds, which in most cases are buried in their protein scaffold deep inside the membrane. Here we used a combination of gel electrophoresis and pull-down assay techniques in conjunction with immunostaining as well as complexome profiling to identify and analyze the composition of assembly intermediates in solubilized membranes of the bacterium Paracoccus denitrificans...
2017: PloS One
https://www.readbyqxmd.com/read/28106854/the-effect-of-polyphenols-on-protein-degradation-pathways-implications-for-neuroprotection
#5
REVIEW
Parvana Hajieva
Human neurodegenerative diseases are accompanied by accumulation of heavily oxidized and aggregated proteins. However, the exact molecular reason is not fully elucidated yet. Insufficient cellular protein quality control is thought to play an important role in accumulating covalently oxidized misfolded proteins. Pharmacologically active polyphenols and their derivatives exhibit potential for preventive and therapeutic purposes against protein aggregation during neurodegeneration. Although these compounds act on various biochemical pathways, their role in stabilizing the protein degradation machinery at different stages may be an attractive therapeutical strategy to halt the accumulation of misfolded proteins...
January 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28106325/a-pde6%C3%AE-kras-inhibitor-chemotype-with-up-to-seven-h-bonds-and-picomolar-affinity-that-prevents-efficient-inhibitor-release-by-arl2
#6
Pablo Martín-Gago, Eyad K Fansa, Christian H Klein, Sandip Murarka, Petra Janning, Marc Schürmann, Malte Metz, Shehab Ismail, Carsten Schultz-Fademrecht, Matthias Baumann, Philippe I H Bastiaens, Alfred Wittinghofer, Herbert Waldmann
Small-molecule inhibition of the interaction between the KRas oncoprotein and the chaperone PDE6δ impairs KRas spatial organization and signaling in cells. However, despite potent binding in vitro (KD <10 nm), interference with Ras signaling and growth inhibition require 5-20 μm compound concentrations. We demonstrate that these findings can be explained by fast release of high-affinity inhibitors from PDE6δ by the release factor Arl2. This limitation is overcome by novel highly selective inhibitors that bind to PDE6δ with up to 7 hydrogen bonds, resulting in picomolar affinity...
January 20, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28106321/conserved-two-component-hik34-rre1-module-directly-activates-heat-stress-inducible-transcription-of-major-chaperone-and-other-genes-in-synechococcus-elongatus-pcc-7942
#7
Ikki Kobayashi, Satoru Watanabe, Yu Kanesaki, Tomohiro Shimada, Hirofumi Yoshikawa, Kan Tanaka
Bacteria and other organisms, including cyanobacteria, employ two-component signal transducing modules comprising histidine kinases and response regulators to acclimate to changing environments. While the number and composition of these modules differ among cyanobacteria, two response regulators that contain DNA binding domains, RpaB and Rre1, are conserved in all sequenced cyanobacterial genomes and are essential for viability. Although RpaB negatively or positively regulates high light and other stress-responsive gene expression, little is known about the function of Rre1...
January 20, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28105855/analysis-of-a549-cell-proteome-alteration-in-response-to-recombinant-influenza-a-virus-nucleoprotein-and-its-interaction-with-cellular-proteins-a-preliminary-study
#8
D Kumar, K Tiwari, M S Rajala
 Influenza A virus undergoes frequent changes of antigenicity and contributes to seasonal epidemics or unpredictable pandemics. Nucleoprotein, encoded by gene segment 5, is an internal protein of the virus and is conserved among strains of different host origins. In the current study, we analyzed the differentially expressed proteins in A549 cells transiently transfected with the recombinant nucleoprotein of influenza A virus by 2D gel electrophoresis. The resolved protein spots on gel were identified by MALDI-TOF/Mass spectrometry analysis...
January 19, 2017: Acta Virologica
https://www.readbyqxmd.com/read/28104585/rcad-bip-pathway-is-necessary-for-the-proper-synthesis-of-digestive-enzymes-and-the-secretory-function-of-the-exocrine-pancreas
#9
Camille Miller, Yafei Cai, Tadd Patton, Sarai Graves, Honglin Li, Maria Eugenia Sabbatini
Alcoholism causes an imbalance of endoplasmic reticulum (ER) homeostasis in pancreatic acini. In those cells, the ER is involved in the synthesis and folding of pancreatic enzymes. Ufm1 (Ubiquitin-fold modifier 1) is part of a novel ubiquitin-like modification system involved in maintaining ER homeostasis. Among the components of the Ufm1 system, Regulator of C53 and DDRGK1 (RCAD) has recently been identified as an Ufm1-specific E3 ligase that promotes ufmylation of DDRGK1, a RCAD-interacting protein. We determined the importance of RCAD in the proper synthesis and secretion of pancreatic enzymes using RCAD-deficient mice...
January 19, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28104576/nitro-fatty-acids-in-plant-signaling-new-key-mediators-of-nitric-oxide-metabolism
#10
REVIEW
Capilla Mata-Pérez, Beatriz Sánchez-Calvo, María N Padilla, Juan C Begara-Morales, Raquel Valderrama, Francisco J Corpas, Juan B Barroso
Recent studies in animal systems have shown that NO can interact with fatty acids to generate nitro-fatty acids (NO2-FAs). They are the product of the reaction between reactive nitrogen species and unsaturated fatty acids, and are considered novel mediators of cell signaling based mainly on a proven anti-inflammatory response. Although these signaling mediators have been described widely in animal systems, NO2-FAs have scarcely been studied in plants. Preliminary data have revealed the endogenous presence of free and protein-adducted NO2-FAs in extra-virgin olive oil (EVOO), which appear to be contributing to the cardiovascular benefits associated with the Mediterranean diet...
January 10, 2017: Redox Biology
https://www.readbyqxmd.com/read/28104494/thoughts-on-interactions-between-pgrmc1-and-diverse-attested-and-potential-hydrophobic-ligands
#11
REVIEW
Michael A Cahill, Amy E Medlock
Progesterone Receptor Membrane Component 1 (PGRMC1) is located in many different subcellular locations with many different attested and probably location-specific functions. PGRMC1 was recently identified in the mitochondrial outer membrane where it interacts with ferrochelatase, the last enzyme in the heme synthetic pathway. It has been proposed that PGRMC1 may act as a chaperone to shuttle newly synthesized heme from the mitochondrion to cytochrome P450 (cyP450) enzymes. Here we consider potential roles that PGRMC1 may play in transferring heme, and other small hydrophobic ligands such as cholesterol and steroids, between the hydrophobic compartment of the membrane lipid bilayer interior to aqueous proteins, and perhaps to the membranes of other organelles...
January 16, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28104372/insights-on-the-structural-dynamics-of-leishmania-braziliensis-hsp90-molecular-chaperone-by-small-angle-x-ray-scattering
#12
Thiago V Seraphim, Kelly P Silva, Paulo R Dores-Silva, Leandro R S Barbosa, Júlio C Borges
Heat shock protein of 90kDa (Hsp90) is an essential molecular chaperone involved in a plethora of cellular activities which modulate protein homeostasis. During the Hsp90 mechanochemical cycle, it undergoes large conformational changes, oscillating between open and closed states. Although structural and conformational equilibria of prokaryotic and some eukaryotic Hsp90s are known, some protozoa Hsp90 structures and dynamics are poorly understood. In this study, we report the solution structure and conformational dynamics of Leishmania braziliensis Hsp90 (LbHsp90) investigated by small angle X-ray scattering (SAXS)...
January 16, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28104284/-fabry-disease
#13
F Stephan, R Haber
Fabry disease, also known as Anderson-Fabry disease or angiokeratoma corporis diffusum universale, is an X-linked recessive form of sphingolipidosis caused by total or partial deficiency of the lysosomal hydrolase, alpha-galactosidase A. From the youngest age, it results in a gradual ubiquitous build-up of glycosphingolipids that are not degraded by the missing enzyme. Cutaneous, neurological, nephrologic, cardiac, gastrointestinal, ophthalmological, respiratory, cochleovestibular and haematological involvement are responsible for increased mortality and significant impairment of quality of life in subjects affected by the disease...
January 16, 2017: Annales de Dermatologie et de Vénéréologie
https://www.readbyqxmd.com/read/28103719/pegylated-nanoliposomal-clusterin-for-amyloidogenic-light-chain-induced-endothelial-dysfunction
#14
Diana Guzman-Villanueva, Raymond Q Migrino, Seth Truran, Nina Karamanova, Daniel A Franco, Camelia Burciu, Subhadip Senapati, Dobrin Nedelkov, Parameswaran Hari, Volkmar Weissig
Light chain (AL) amyloidosis is a disease associated with significant morbidity and mortality arising from multi-organ injury induced by amyloidogenic light chain proteins (LC). There is no available treatment to reverse the toxicity of LC. We previously showed that chaperone glycoprotein clusterin (CLU) and nanoliposomes (NL), separately, restore human microvascular endothelial function impaired by LC. In this work, we aim to prepare PEGylated-nanoliposomal clusterin (NL-CLU) formulations that could allow combined benefit against LC while potentially enabling efficient delivery to microvascular tissue, and test efficacy on human arteriole endothelial function...
January 20, 2017: Journal of Liposome Research
https://www.readbyqxmd.com/read/28102850/japanese-encephalitis-virus-induces-human-neural-stem-progenitor-cell-death-by-elevating-grp78-phb-and-hnrnpc-through-er-stress
#15
Sriparna Mukherjee, Noopur Singh, Nabonita Sengupta, Mahar Fatima, Pankaj Seth, Anita Mahadevan, Susarla Krishna Shankar, Arindam Bhattacharyya, Anirban Basu
Japanese encephalitis virus (JEV), which is a causative agent of sporadic encephalitis, harbours itself inside the neural stem/progenitor cells. It is a well-known fact that JEV infects neural stem/progenitor cells and decreases their proliferation capacity. With mass spectrometry-based quantitative proteomic study, it is possible to reveal the impact of virus on the stem cells at protein level. Our aim was to perceive the stem cell proteomic response upon viral challenge. We performed a two-dimensional gel electrophoresis-based proteomic study of the human neural stem cells (hNS1 cell line) post JEV infection and found that 13 proteins were differentially expressed...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102469/lanosterol-suppresses-the-aggregation-and-cytotoxicity-of-misfolded-proteins-linked-with-neurodegenerative-diseases
#16
Arun Upadhyay, Ayeman Amanullah, Ribhav Mishra, Amit Kumar, Amit Mishra
Accumulation of misfolded or aberrant proteins in neuronal cells is linked with neurodegeneration and other pathologies. Which molecular mechanisms fail and cause inappropriate folding of proteins and what is their relationship to cellular toxicity is not well known. How does it happen and what are the probable therapeutic or molecular approaches to counter them are also not clear. Here, we demonstrate that treatment of lanosterol diminishes aberrant proteotoxic aggregation and mitigates their cytotoxicity via induced expression of co-chaperone CHIP and elevated autophagy...
January 19, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28101870/fibrillar-collagens
#17
Jordi Bella, David J S Hulmes
Fibrillar collagens (types I, II, III, V, XI, XXIV and XXVII) constitute a sub-group within the collagen family (of which there are 28 types in humans) whose functions are to provide three-dimensional frameworks for tissues and organs. These networks confer mechanical strength as well as signalling and organizing functions through binding to cellular receptors and other components of the extracellular matrix (ECM). Here we describe the structure and assembly of fibrillar collagens, and their procollagen precursors, from the molecular to the tissue level...
2017: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/28101866/titin-and-nebulin-in-thick-and-thin-filament-length-regulation
#18
Larissa Tskhovrebova, John Trinick
In this review we discuss the history and the current state of ideas related to the mechanism of size regulation of the thick (myosin) and thin (actin) filaments in vertebrate striated muscles. Various hypotheses have been considered during of more than half century of research, recently mostly involving titin and nebulin acting as templates or 'molecular rulers', terminating exact assembly. These two giant, single-polypeptide, filamentous proteins are bound in situ along the thick and thin filaments, respectively, with an almost perfect match in the respective lengths and structural periodicities...
2017: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/28101863/lessons-from-animal-models-of-cytoplasmic-intermediate-filament-proteins
#19
Jamal-Eddine Bouameur, Thomas M Magin
Cytoplasmic intermediate filaments (IFs) represent a major cytoskeletal network contributing to cell shape, adhesion and migration as well as to tissue resilience and renewal in numerous bilaterians, including mammals. The observation that IFs are dispensable in cultured mammalian cells, but cause tissue-specific, life-threatening disorders, has pushed the need to investigate their function in vivo. In keeping with human disease, the deletion or mutation of murine IF genes resulted in highly specific pathologies...
2017: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/28100837/erad-icating-mutant-insulin-promotes-functional-insulin-secretion
#20
Daniel J Moore
Overexpression of a chaperone protein liberates functional insulin from a misfolded mutant partner to improve insulin secretion.
January 18, 2017: Science Translational Medicine
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