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https://www.readbyqxmd.com/read/28920507/navigating-the-structure-function-evolutionary-relationship-of-csaa-chaperone-in-archaea
#1
Archana Sharma, Shikha Rani, Manisha Goel
CsaA is a protein involved in the post-translational translocation of proteins across the cytoplasmic membrane. It is considered to be a functional homolog of SecB which participates in the Sec-dependent translocation pathway in an analogous manner. CsaA has also been reported to act as a molecular chaperone, preventing aggregation of unfolded proteins. It is essentially a prokaryotic protein which is absent in eukaryotes, but found extensively in bacteria and earlier thought to be widely present in archaea...
September 18, 2017: Critical Reviews in Microbiology
https://www.readbyqxmd.com/read/28919881/genomic-and-transcriptomic-analysis-of-growth-supporting-dehalogenation-of-chlorinated-methanes-in-methylobacterium
#2
Pauline Chaignaud, Bruno Maucourt, Marion Weiman, Adriana Alberti, Steffen Kolb, Stéphane Cruveiller, Stéphane Vuilleumier, Françoise Bringel
Bacterial adaptation to growth with toxic halogenated chemicals was explored in the context of methylotrophic metabolism of Methylobacterium extorquens, by comparing strains CM4 and DM4, which show robust growth with chloromethane and dichloromethane, respectively. Dehalogenation of chlorinated methanes initiates growth-supporting degradation, with intracellular release of protons and chloride ions in both cases. The core, variable and strain-specific genomes of strains CM4 and DM4 were defined by comparison with genomes of non-dechlorinating strains...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28919577/some-properties-of-three-%C3%AE-b-crystallin-mutants-carrying-point-substitutions-in-the-c-terminal-domain-and-associated-with-congenital-diseases
#3
Evgenia S Gerasimovich, Sergei V Strelkov, Nikolai B Gusev
Physico-chemical properties of G154S, R157H and A171T mutants of αB-crystallin (HspB5) associated with congenital human diseases including certain myopathies and cataract were investigated. Oligomers formed by G154S and A171T mutants have the size and apparent molecular weight indistinguishable from those of the wild-type HspB5, whereas the size of oligomers formed by R157H mutant is slightly smaller. All mutants are less thermostable and start to aggregate at a lower temperature than the wild-type protein...
September 14, 2017: Biochimie
https://www.readbyqxmd.com/read/28919234/effects-of-periplasmic-chaperones-and-membrane-thickness-on-bama-catalysed-outer-membrane-protein-folding
#4
Bob Schiffrin, Antonio N Calabrese, Anna J Higgins, Julia R Humes, Alison E Ashcroft, Antreas C Kalli, David J Brockwell, Sheena E Radford
The biogenesis of outer membrane proteins (OMPs) in Gram-negative bacteria involves delivery by periplasmic chaperones to the β-barrel assembly machinery (BAM) which catalyses OMP insertion into the outer membrane (OM). Here, we examine the effects of membrane thickness, the E. coli periplasmic chaperones Skp and SurA, and BamA, the central subunit of the BAM complex, on the folding kinetics of a model OMP (tOmpA) using fluorescence spectroscopy, native mass spectrometry, and molecular dynamics (MD) simulations...
September 15, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28919078/slp1-emp65-a-guardian-factor-that-protects-folding-polypeptides-from-promiscuous-degradation
#5
Shan Zhang, Chengchao Xu, Katherine E Larrimore, Davis T W Ng
Newly synthesized proteins engage molecular chaperones that assist folding. Their progress is monitored by quality control systems that target folding errors for degradation. Paradoxically, chaperones that promote folding also direct unfolded polypeptides for degradation. Hence, a mechanism was previously hypothesized that prevents the degradation of actively folding polypeptides. In this study, we show that a conserved endoplasmic reticulum (ER) membrane protein complex, consisting of Slp1 and Emp65 proteins, performs this function in the ER lumen...
September 11, 2017: Cell
https://www.readbyqxmd.com/read/28915917/translocation-of-molecular-chaperones-to-the-titin-springs-is-common-in-skeletal-myopathy-patients-and-affects-sarcomere-function
#6
Andreas Unger, Lisa Beckendorf, Pierre Böhme, Rudolf Kley, Marion von Frieling-Salewsky, Hanns Lochmüller, Rolf Schröder, Dieter O Fürst, Matthias Vorgerd, Wolfgang A Linke
Myopathies encompass a wide variety of acquired and hereditary disorders. The pathomechanisms include structural and functional changes affecting, e.g., myofiber metabolism and contractile properties. In this study, we observed increased passive tension (PT) of skinned myofibers from patients with myofibrillar myopathy (MFM) caused by FLNC mutations (MFM-filaminopathy) and limb-girdle muscular dystrophy type-2A due to CAPN3 mutations (LGMD2A), compared to healthy control myofibers. Because the giant protein titin determines myofiber PT, we measured its molecular size and the titin-to-myosin ratio, but found no differences between myopathies and controls...
September 15, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28914785/hsp90%C3%AE-mediates-bmi1-expression-in-breast-cancer-stem-progenitor-cells-through-facilitating-nuclear-translocation-of-c-myc-and-ezh2
#7
Yueh-Chun Lee, Wen-Wei Chang, Yi-Ying Chen, Yu-Hung Tsai, Ying-Hsiang Chou, Hsien-Chun Tseng, Hsin-Lin Chen, Chun-Chieh Wu, Ju Chang-Chien, Hsueh-Te Lee, Huei-Fan Yang, Bing-Yen Wang
Heat shock protein 90 (Hsp90) is a molecular chaperone that facilitates the correct folding and functionality of its client protein. Numerous Hsp90-client proteins are involved in cancer development. Thus, Hsp90 inhibitors have potential applications as anti-cancer drugs. We previously discovered that Hsp90α expression increased in breast cancer stem cells (BCSCs), which can initiate tumorigenesis and metastasis and resist treatment. In the present study, we further demonstrated that 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), an inhibitor of Hsp90, could suppress the self-renewal of BCSCs by downregulating B lymphoma Mo-MLV insertion region 1 homolog (BMI1), a polycomb family member with oncogenic activity in breast cancer...
September 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28914774/targeting-heat-shock-proteins-in-cancer-a-promising-therapeutic-approach
#8
REVIEW
Suman Chatterjee, Timothy F Burns
Heat shock proteins (HSPs) are a large family of chaperones that are involved in protein folding and maturation of a variety of "client" proteins protecting them from degradation, oxidative stress, hypoxia, and thermal stress. Hence, they are significant regulators of cellular proliferation, differentiation and strongly implicated in the molecular orchestration of cancer development and progression as many of their clients are well established oncoproteins in multiple tumor types. Interestingly, tumor cells are more HSP chaperonage-dependent than normal cells for proliferation and survival because the oncoproteins in cancer cells are often misfolded and require augmented chaperonage activity for correction...
September 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28913005/chaperone-based-therapies-for-disease-modification-in-parkinson-s-disease
#9
REVIEW
Erik L Friesen, Mitch L De Snoo, Luckshi Rajendran, Lorraine V Kalia, Suneil K Kalia
Parkinson's disease (PD) is the second most common neurodegenerative disorder and is characterized by the presence of pathological intracellular aggregates primarily composed of misfolded α-synuclein. This pathology implicates the molecular machinery responsible for maintaining protein homeostasis (proteostasis), including molecular chaperones, in the pathobiology of the disease. There is mounting evidence from preclinical and clinical studies that various molecular chaperones are downregulated, sequestered, depleted, or dysfunctional in PD...
2017: Parkinson's Disease
https://www.readbyqxmd.com/read/28911862/fatty-acid-binding-protein-fabp-5-interacts-with-the-calnexin-cytoplasmic-domain-at-the-endoplasmic-reticulum
#10
Joanna Jung, Jessica Wang, Jody Groenendyk, Dukgyu Lee, Marek Michalak, Luis B Agellon
Calnexin is a type 1 integral endoplasmic reticulum membrane molecular chaperone with an endoplasmic reticulum luminal chaperone domain and a highly conserved C-terminal domain oriented to the cytoplasm. Fabp5 is a cytoplasmic protein that binds long-chain fatty acids and other lipophilic ligands. Using a yeast two-hybrid screen, immunoprecipitation, microscale thermophoresis analysis and cellular fractionation, we discovered that Fabp5 interacts with the calnexin cytoplasmic C-tail domain at the endoplasmic reticulum...
September 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28911813/functional-dynamics-in-cyclic-nucleotide-signaling-and-amyloid-inhibition
#11
REVIEW
Bryan VanSchouwen, Rashik Ahmed, Julijana Milojevic, Giuseppe Melacini
It is now established that understanding the molecular basis of biological function requires atomic resolution maps of both structure and dynamics. Here, we review several illustrative examples of functional dynamics selected from our work on cyclic nucleotide signaling and amyloid inhibition. Although fundamentally diverse, a central aspect common to both fields is that function can only be rationalized by considering dynamic equilibria between distinct states of the accessible free energy landscape. The dynamic exchange between ground and excited states of signaling proteins is essential to explain auto-inhibition and allosteric activation...
September 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28910138/hsp90-inhibition-and-cellular-stress-elicits-phenotypic-plasticity-in-hematopoietic-differentiation
#12
Abdalla A Lawag, Jennifer M Napper, Caroline A Hunter, Nickolas A Bacon, Seth Deskins, Manaf El-Hamdani, Sarah-Leigh Govender, Emine C Koc, Vincent E Sollars
Cancer cells exist in a state of Darwinian selection using mechanisms that produce changes in gene expression through genetic and epigenetic alteration to facilitate their survival. Cellular plasticity, or the ability to alter cellular phenotype, can assist in survival of premalignant cells as they progress to full malignancy by providing another mechanism of adaptation. The connection between cellular stress and the progression of cancer has been established, although the details of the mechanisms have yet to be fully elucidated...
September 14, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28906057/a-chemical-disruptor-of-the-clpx-chaperone-complex-attenuates-multiresistant-staphylococcus-aureus-virulence
#13
Christian Fetzer, Vadim S Korotkov, Robert Thänert, Kyu Myung Lee, Martin Neuenschwander, Jens Peter von Kries, Eva Medina, Stephan Axel Sieber
The Staphylococcus aureus ClpXP protease is an important regulator of cell homeostasis and virulence. Here we utilize a high-throughput screen against the ClpXP complex and identify a specific inhibitor of the ClpX chaperone that disrupts its oligomeric state. Synthesis of 34 derivatives revealed that the molecular scaffold is restrictive for diversification with only minor changes tolerated. Subsequent analysis of the most active compound revealed strong attenuation of S. aureus toxin production which was quantified via a customized MS-based assay platform...
September 14, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28905214/mir-217-5p-induces-apoptosis-by-directly-targeting-prkci-bag3-itgav-and-mapk1-in-colorectal-cancer-cells
#14
Marion Flum, Michael Kleemann, Helga Schneider, Benjamin Weis, Simon Fischer, René Handrick, Kerstin Otte
Apoptosis is a genetically directed process of programmed cell death. A variety of microRNAs (miRNAs), endogenous single-stranded non-coding RNAs of about 22 nucleotides in length have been shown to be involved in the regulation of the intrinsic or extrinsic apoptotic pathways. There is increasing evidence that the aberrant expression of miRNAs plays a causal role in the development of diseases such as cancer. This makes miRNAs promising candidate molecules as therapeutic targets or agents. MicroRNA (miR)-217-5p has been implicated in carcinogenesis of various cancer entities, including colorectal cancer...
September 14, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28903051/features-of-the-chaperone-cellular-network-revealed-through-systematic-interaction-mapping
#15
Kamran Rizzolo, Jennifer Huen, Ashwani Kumar, Sadhna Phanse, James Vlasblom, Yoshito Kakihara, Hussein A Zeineddine, Zoran Minic, Jamie Snider, Wen Wang, Carles Pons, Thiago V Seraphim, Edgar Erik Boczek, Simon Alberti, Michael Costanzo, Chad L Myers, Igor Stagljar, Charles Boone, Mohan Babu, Walid A Houry
A comprehensive view of molecular chaperone function in the cell was obtained through a systematic global integrative network approach based on physical (protein-protein) and genetic (gene-gene or epistatic) interaction mapping. This allowed us to decipher interactions involving all core chaperones (67) and cochaperones (15) of Saccharomyces cerevisiae. Our analysis revealed the presence of a large chaperone functional supercomplex, which we named the naturally joined (NAJ) chaperone complex, encompassing Hsp40, Hsp70, Hsp90, AAA+, CCT, and small Hsps...
September 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/28901511/n%C3%A2-acetylcysteine-induces-apoptosis-via-the-mitochondria%C3%A2-dependent-pathway-but-not-via-endoplasmic-reticulum-stress-in-h9c2-cells
#16
Yuyong Liu, Ke Liu, Nian Wang, Huali Zhang
N‑acetylcysteine (NAC), a precursor of glutathione, is a widely used thiol‑containing antioxidant and modulator of the intracellular redox state. Our previous study demonstrated that excess reduced glutathione (GSH) from NAC treatment paradoxically led to a reduction in glutathione redox potential, increased mitochondrial oxidation and caused cytotoxicity at lower reactive oxygen species levels in H9c2 cells. However, no detailed data are available on the molecular mechanisms of NAC‑induced cytotoxicity on H9c2 cells...
September 8, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28900229/a-class-ii-small-heat-shock-protein-oshsp18-0-plays-positive-roles-in-both-biotic-and-abiotic-defense-responses-in-rice
#17
Jie Kuang, Jianzhong Liu, Jun Mei, Changchun Wang, Haitao Hu, Yanjun Zhang, Meihao Sun, Xi Ning, Langtao Xiao, Ling Yang
Bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most devastating diseases of rice. However, the molecular mechanism underpinning the Xoo resistance of rice is still not fully understood. Here, we report that a class II small heat shock protein gene, OsHsp18.0, whose expression was differentially induced between a resistant and a susceptible variety in response to Xoo infection, plays positive roles in both biotic and abiotic resistance. The molecular chaperone activity of OsHsp18...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28900031/the-metal-chaperone-atox1-regulates-the-activity-of-the-human-copper-transporter-atp7b-by-modulating-domain-dynamics
#18
Corey H Yu, Nan Yang, Jameson Bothe, Marco Tonelli, Sergiy Nokhrin, Natalia V Dolgova, Lelita T Braiterman, Svetlana Lutsenko, Oleg Y Dmitriev
The human transporter ATP7B delivers copper to the biosynthetic pathways and maintains copper homeostasis in the liver. Mutations in ATP7B cause the potentially fatal hepato-neurological disorder Wilson disease. The activity and intracellular localization of ATP7B are regulated by copper, but the molecular mechanism of this regulation is largely unknown. We show that the copper chaperone Atox1, which delivers copper to ATP7B, and the group of the first three metal binding domains (MBD1-3) are central to the activity regulation of ATP7B...
September 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28898250/effects-of-proteasome-inhibitor-mg-132-on-the-parasite-schistosoma-mansoni
#19
Enyara R Morais, Katia C Oliveira, Renato G de Paula, Alice M M Ornelas, Érika B C Moreira, Fernanda Rafacho Badoco, Lizandra G Magalhães, Sergio Verjovski-Almeida, Vanderlei Rodrigues
Proteasome is a proteolytic complex responsible for intracellular protein turnover in eukaryotes, archaea and in some actinobacteria species. Previous work has demonstrated that in Schistosoma mansoni parasites, the proteasome inhibitor MG-132 affects parasite development. However, the molecular targets affected by MG-132 in S. mansoni are not entirely known. Here, we used expression microarrays to measure the genome-wide changes in gene expression of S. mansoni adult worms exposed in vitro to MG-132, followed by in silico functional analyses of the affected genes using Ingenuity Pathway Analysis (IPA)...
2017: PloS One
https://www.readbyqxmd.com/read/28895938/functional-amyloid-protection-in-the-eye-lens-retention-of-%C3%AE-crystallin-molecular-chaperone-activity-after-modification-into-amyloid-fibrils
#20
Megan Garvey, Heath Ecroyd, Nicholas J Ray, Juliet A Gerrard, John A Carver
Amyloid fibril formation occurs from a wide range of peptides and proteins and is typically associated with a loss of protein function and/or a gain of toxic function, as the native structure of the protein undergoes major alteration to form a cross β-sheet array. It is now well recognised that some amyloid fibrils have a biological function, which has led to increased interest in the potential that these so-called functional amyloids may either retain the function of the native protein, or gain function upon adopting a fibrillar structure...
September 12, 2017: Biomolecules
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