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Chaperones

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https://www.readbyqxmd.com/read/28449065/a-homozygous-missense-mutation-in-eral1-encoding-a-mitochondrial-rrna-chaperone-causes-perrault-syndrome
#1
Iliana A Chatzispyrou, Marielle Alders, Sergio Guerrero-Castillo, Ruben Zapata Perez, Martin A Haagmans, Laurent Mouchiroud, Janet Koster, Rob Ofman, Frank Baas, Hans R Waterham, Johannes N Spelbrink, Johan Auwerx, Marcel M Mannens, Riekelt H Houtkooper, Astrid S Plomp
Perrault syndrome (PS) is a rare recessive disorder characterized by ovarian dysgenesis and sensorineural deafness. It is clinically and genetically heterogeneous, and previously mutations have been described in different genes, mostly related to mitochondrial proteostasis. We diagnosed three unrelated females with PS and set out to identify the underlying genetic cause using exome sequencing. We excluded mutations in the known PS genes, but identified a single homozygous mutation in the ERAL1 gene (c.707A>T; p...
April 25, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28448559/hexa-is-a-versatile-regulator-involved-in-the-control-of-phenotypic-heterogeneity-of-photorhabdus-luminescens
#2
Angela Langer, Adriana Moldovan, Christian Harmath, Susan A Joyce, David J Clarke, Ralf Heermann
Phenotypic heterogeneity in microbial communities enables genetically identical organisms to behave differently even under the same environmental conditions. Photorhabdus luminescens, a bioluminescent Gram-negative bacterium, contains a complex life cycle, which involves a symbiotic interaction with nematodes as well as a pathogenic association with insect larvae. P. luminescens exists in two distinct phenotypic cell types, designated as the primary (1°) and secondary (2°) cells. The 1° cells are bioluminescent, pigmented and can support nematode growth and development...
2017: PloS One
https://www.readbyqxmd.com/read/28445802/nmnat-it-s-an-nad-synthase%C3%A2-it-s-a-chaperone%C3%A2-it-s-a-neuroprotector
#3
REVIEW
Jennifer M Brazill, Chong Li, Yi Zhu, R Grace Zhai
Nicotinamide mononucleotide adenylyl transferases (NMNATs) are a family of highly conserved proteins indispensable for cellular homeostasis. NMNATs are classically known for their enzymatic function of catalyzing NAD(+) synthesis, but also have gained a reputation as essential neuronal maintenance factors. NMNAT deficiency has been associated with various human diseases with pronounced consequences on neural tissues, underscoring the importance of the neuronal maintenance and protective roles of these proteins...
April 23, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28445721/nacho-mediates-nicotinic-acetylcholine-receptor-function-throughout-the-brain
#4
Jose A Matta, Shenyan Gu, Weston B Davini, Brian Lord, Edward R Siuda, Anthony W Harrington, David S Bredt
Neuronal nicotinic acetylcholine receptors (nAChRs) participate in diverse aspects of brain function and mediate behavioral and addictive properties of nicotine. Neuronal nAChRs derive from combinations of α and β subunits, whose assembly is tightly regulated. NACHO was recently identified as a chaperone for α7-type nAChRs. Here, we find NACHO mediates assembly of all major classes of presynaptic and postsynaptic nAChR tested. NACHO acts at early intracellular stages of nAChR subunit assembly and then synergizes with RIC-3 for receptor surface expression...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445720/hsp90-is-essential-under-heat-stress-in-the-bacterium-shewanella-oneidensis
#5
Flora Ambre Honoré, Vincent Méjean, Olivier Genest
The Hsp90 chaperone is essential in eukaryotes and activates a large array of client proteins. In contrast, its role is still elusive in bacteria, and only a few Hsp90 bacterial clients are known. Here, we found that Hsp90 is essential in the model bacterium Shewanella oneidensis under heat stress. A genetic screen for Hsp90 client proteins identified TilS, an essential protein involved in tRNA maturation. Overexpression of TilS rescued the growth defect of the hsp90 deletion strain under heat stress. In vivo, the activity and the amount of TilS were significantly reduced in the absence of Hsp90 at high temperature...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28443462/biib021-a-novel-inhibitor-to-heat-shock-protein-90-addicted-oncology
#6
Liang Yan, Weiming Zhang, Beibei Zhang, Chao Xuan, Daogang Wang
Heat shock protein 90 is induced in response to the cell stress. Its overexpression has been reported in many cancers with poor prognosis. It acts as a chaperone to the client proteins, especially the activated oncoproteins in malignancies to protect them from degradation. Heat shock protein 90 inhibition represented anti-cancer effects in many studies. Previous natural product-based compounds are limited by their association with target toxicities. BIIB021 is an orally available, fully synthetic novel small-molecule heat shock protein 90 inhibitor that has shown strong antitumor activities in a large number of preclinical models and is now under clinical investigation...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28443288/rubisco-activases-aaa-chaperones-adapted-to-enzyme-repair
#7
REVIEW
Javaid Y Bhat, Gabriel Thieulin-Pardo, F Ulrich Hartl, Manajit Hayer-Hartl
Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), the key enzyme of the Calvin-Benson-Bassham cycle of photosynthesis, requires conformational repair by Rubisco activase for efficient function. Rubisco mediates the fixation of atmospheric CO2 by catalyzing the carboxylation of the five-carbon sugar ribulose-1,5-bisphosphate (RuBP). It is a remarkably inefficient enzyme, and efforts to increase crop yields by bioengineering Rubisco remain unsuccessful. This is due in part to the complex cellular machinery required for Rubisco biogenesis and metabolic maintenance...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28443118/the-absence-of-the-arabidopsis-chaperone-complex-caf-1-produces-mitotic-chromosome-abnormalities-and-changes-in-the-expression-profiles-of-genes-involved-in-dna-repair
#8
Javier Varas, Juan L Santos, Mónica Pradillo
Chromatin Assembly Factor 1 (CAF-1) is an evolutionary conserved heterotrimeric chaperone complex that facilitates the incorporation of histones H3 and H4 onto newly synthesized DNA. We demonstrate here that the mutant deficient for the large subunit of the complex, fas1-4, and in minor extent, the mutant deficient for the middle subunit, fas2-1, display chromosome abnormalities throughout Arabidopsis mitosis. Among them, we observed multicentromeric chromosomes at metaphase, and chromatid bridges and acentric fragments at anaphase-telophase...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28442449/comparative-proteomics-of-hydatid-fluids-from-two-echinococcus-multilocularis-isolates
#9
Karina M Monteiro, Karina R Lorenzatto, Jeferson C de Lima, Guilherme B Dos Santos, Sabine Förster, Gabriela P Paludo, Paulo C Carvalho, Klaus Brehm, Henrique B Ferreira
The hydatid fluid (HF) that fills Echinococcus multilocularis metacestode vesicles is a complex mixture of proteins from both parasite and host origin. Here, a LC-MS/MS approach was used to compare the HF composition of E. multilocularis H95 and G8065 isolates (EmH95 and EmG8065, respectively), which present differences in terms of growth and fertility. Overall, 446 unique proteins were identified, 392 of which (88%) were from parasite origin and 54 from culture medium. At least 256 of parasite proteins were sample exclusive, and 61 of the 136 shared proteins presented differential abundance between E...
April 22, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28442254/copalic-acid-analogs-down-regulate-androgen-receptor-and-inhibit-small-chaperone-protein
#10
Nethrie D Idippily, Qiaoyun Zheng, Chunfang Gan, Aicha Quamine, Morgan M Ashcraft, Bo Zhong, Bin Su
Copalic acid, one of the diterpenoid acids in copaiba oil, inhibited the chaperone function of α-crystallin and heat shock protein 27kD (HSP27). It also showed potent activity in decreasing an HSP27 client protein, androgen receptor (AR), which makes it useful in prostate cancer treatment or prevention. To develop potent drug candidates to decrease the AR level in prostate cancer cells, more copalic acid analogs were synthesized. Using the level of AR as the readout, 15 of the copalic acid analogs were screened and two compounds were much more potent than copalic acid...
April 13, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28441058/protein-misfolding-diseases
#11
F Ulrich Hartl
The majority of protein molecules must fold into defined three-dimensional structures to acquire functional activity. However, protein chains can adopt a multitude of conformational states, and their biologically active conformation is often only marginally stable. Metastable proteins tend to populate misfolded species that are prone to forming toxic aggregates, including soluble oligomers and fibrillar amyloid deposits, which are linked with neurodegeneration in Alzheimer and Parkinson disease, and many other pathologies...
April 24, 2017: Annual Review of Biochemistry
https://www.readbyqxmd.com/read/28439947/sirt1-hsf1-hsps-pathway-is-essential-for-exenatide-alleviated-lipid-induced-hepatic-endoplasmic-reticulum-stress
#12
Xiaobin Zheng, Fen Xu, Hua Liang, Huanyi Cao, Mengyin Cai, Wen Xu, Jianping Weng
Recent studies have indicated lipid-induced endoplasmic reticulum (ER) stress to be a major contributor to the progression of hepatic steatosis. Exenatide (Exendin-4), a glucagon-like peptide-1 receptor agonist, is known to improve hepatic steatosis with accumulating evidence. In this study, we investigated whether exenatide could alleviate lipid-induced hepatic ER stress through mammal sirtuin1 (SIRT1) and illustrated the detailed mechanisms. Male C57BL/6J mice challenged with a high-fat diet (HFD) were then treated with exenatide or normal saline by intraperitoneal injection for 4 weeks...
April 25, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28438648/the-superoxide-dismutase-mimetic-tempol-blunts-diabetes-induced-upregulation-of-nadph-oxidase-and-endoplasmic-reticulum-stress-in-a-rat-model-of-diabetic-nephropathy
#13
Miles J De Blasio, Anand Ramalingam, Anh H Cao, Darnel Prakoso, Ji-Ming Ye, Raelene Pickering, Anna M D Watson, Judy B de Haan, David M Kaye, Rebecca H Ritchie
Endoplasmic reticulum (ER) stress contributes to progression of diabetic nephropathy, which promotes end-stage renal failure in diabetic patients. This study was undertaken to investigate the actions of tempol and ramipril, pharmacological agents that target the consequences of NADPH oxidase, on diabetic nephropathy in a rat model of type 1 diabetes, with an emphasis on markers of ER stress. Male Sprague-Dawley rats were injected intravenously with a single bolus of streptozotocin (55mg/kg) to induce type 1 diabetes...
April 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28438176/the-pink1-p-i368n-mutation-affects-protein-stability-and-ubiquitin-kinase-activity
#14
Maya Ando, Fabienne C Fiesel, Roman Hudec, Thomas R Caulfield, Kotaro Ogaki, Paulina Górka-Skoczylas, Dariusz Koziorowski, Andrzej Friedman, Li Chen, Valina L Dawson, Ted M Dawson, Guojun Bu, Owen A Ross, Zbigniew K Wszolek, Wolfdieter Springer
BACKGROUND: Mutations in PINK1 and PARKIN are the most common causes of recessive early-onset Parkinson's disease (EOPD). Together, the mitochondrial ubiquitin (Ub) kinase PINK1 and the cytosolic E3 Ub ligase PARKIN direct a complex regulated, sequential mitochondrial quality control. Thereby, damaged mitochondria are identified and targeted to degradation in order to prevent their accumulation and eventually cell death. Homozygous or compound heterozygous loss of either gene function disrupts this protective pathway, though at different steps and by distinct mechanisms...
April 24, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28438025/fusion-of-polymeric-material-binding-peptide-to-cell-adhesion-artificial-proteins-enhances-their-biological-function
#15
Tomonori Waku, Yuko Imanishi, Yuta Yoshino, Shigeru Kunugi, Takeshi Serizawa, Naoki Tanaka
Orientation-controlled protein immobilization on a solid substrate surface is important for the development of biomedical materials such as scaffolds used in tissue engineering. In this study, the authors demonstrated that the introduction of material-binding peptides (MBPs) in Arg-Gly-Asp (RGD)-fused artificial proteins called blocking peptide fragment (BPF), which are fragments (residues 419-607) of the molecular chaperone DnaK, enhances the oriented adsorption of proteins on the polymer surface and improves their cell adhesion capability...
April 24, 2017: Biointerphases
https://www.readbyqxmd.com/read/28437479/conformational-dynamics-of-bacterial-trigger-factor-in-apo-and-ribosome-bound-states
#16
Mehmet Tarik Can, Zeynep Kurkcuoglu, Gokce Ezeroglu, Arzu Uyar, Ozge Kurkcuoglu, Pemra Doruker
The chaperone trigger factor (TF) binds to the ribosome exit tunnel and helps cotranslational folding of nascent chains (NC) in bacterial cells and chloroplasts. In this study, we aim to investigate the functional dynamics of fully-atomistic apo TF and its complex with 50S. As TF accomodates a high percentage of charged residues on its surface, the effect of ionic strength on TF dynamics is assessed here by performing five independent molecular dynamics (MD) simulations (total of 1.3 micro-second duration) at 29 mM and 150 mM ionic strengths...
2017: PloS One
https://www.readbyqxmd.com/read/28437467/mutant-uromodulin-expression-leads-to-altered-homeostasis-of-the-endoplasmic-reticulum-and-activates-the-unfolded-protein-response
#17
Céline Schaeffer, Stefania Merella, Elena Pasqualetto, Dejan Lazarevic, Luca Rampoldi
Uromodulin is the most abundant urinary protein in physiological conditions. It is exclusively produced by renal epithelial cells lining the thick ascending limb of Henle's loop (TAL) and it plays key roles in kidney function and disease. Mutations in UMOD, the gene encoding uromodulin, cause autosomal dominant tubulointerstitial kidney disease uromodulin-related (ADTKD-UMOD), characterised by hyperuricemia, gout and progressive loss of renal function. While the primary effect of UMOD mutations, retention in the endoplasmic reticulum (ER), is well established, its downstream effects are still largely unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28436221/the-iron-chaperone-protein-cyay-from-vibrio-cholerae-is-a-heme-binding-protein
#18
Takeshi Uchida, Noriyuki Kobayashi, Souichiro Muneta, Koichiro Ishimori
CyaY is an iron transport protein for Fe-S cluster biosynthetic systems and a ferrochelatase that catalyzes insertion of Fe(2+) into protoporphyrin IX. Here, we found that CyaY has the ability to bind heme as well as iron, exhibiting a dissociation constant for heme of 21 ± 6 nM. Absorption and resonance Raman spectra revealed that both ferric and ferrous forms of heme were bound to an anionic ligand (e.g., tyrosine and/or cysteine). Consistent with this, mutagenesis studies showed that Tyr67 and Cys78 are possible heme ligands of CyaY...
April 24, 2017: Biochemistry
https://www.readbyqxmd.com/read/28434875/covalent-protein-labeling-at-glutamic-acids
#19
Pablo Martín-Gago, Eyad K Fansa, Michael Winzker, Sandip Murarka, Petra Janning, Carsten Schultz-Fademrecht, Matthias Baumann, Alfred Wittinghofer, Herbert Waldmann
Covalent labeling of amino acids in proteins by reactive small molecules, in particular at cysteine SH and lysine NH groups, is a powerful approach to identify and characterize proteins and their functions. However, for the less-reactive carboxylic acids present in Asp and Glu, hardly any methodology is available. Employing the lipoprotein binding chaperone PDE6δ as an example, we demonstrate that incorporation of isoxazolium salts that resemble the structure and reactivity of Woodward's reagent K into protein ligands provides a novel method for selective covalent targeting of binding site carboxylic acids in whole proteomes...
April 13, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28434325/antiamyloidogenic-and-proamyloidogenic-chaperone-effects-of-c-reactive-protein-and-serum-amyloid-p-component
#20
Daisaku Ozawa, Ryo Nomura, P Patrizia Mangione, Kazuhiro Hasegawa, Tadakazu Okoshi, Riccardo Porcari, Vittorio Bellotti, Hironobu Naiki
No abstract text is available yet for this article.
March 2017: Amyloid: the International Journal of Experimental and Clinical Investigation
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