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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
#1
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/28526855/gut-homeostasis-and-regulatory-t-cell-induction-depend-on-molecular-chaperone-gp96-in-cd11c-cells
#2
Yunpeng Hua, Yi Yang, Shaoli Sun, Stephen Iwanowycz, Caroline Westwater, Boris Reizis, Zihai Li, Bei Liu
The intestinal immunity and tolerance are orchestrated by both the innate and the adaptive immune system. Intestinal professional antigen presenting cells (pAPCs) recognize and respond to the gut microbiota through multiple pattern-recognition receptors, including TLRs and NLRs. How gut pAPCs maintain mucosal homeostasis remains incompletely understood. Heat shock protein gp96, also known as grp94, is an essential immune chaperone for TLRs. However, the role of gp96 in regulating CD11c(+) APCs in the gut immunity and tolerance is unknown...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526614/human-aldehyde-dehydrogenase-3a1-aldh3a1-exhibits-chaperone-like-function
#3
Georgia-Persephoni Voulgaridou, Ilias Tsochantaridis, Theodora Mantso, Rodrigo Franco, Mihalis I Panayiotidis, Aglaia Pappa
Aldehyde dehydrogenase 3A1 (ALDH3A1) is a metabolic enzyme that catalyzes the oxidation of various aldehydes. Certain types of epithelial tissues in mammals, especially those continually exposed to environmental stress (e.g., corneal epithelium), express ALDH3A1 at high levels and its abundance in such tissues is perceived to help to maintain cellular homeostasis under conditions of oxidative stress. Metabolic as well as non-metabolic roles for ALDH3A1 have been associated with its mediated resistance to cellular oxidative stress...
May 16, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28510050/a-review-of-multi-domain-and-flexible-molecular-chaperones-studies-by-small-angle-x-ray-scattering
#4
REVIEW
Júlio C Borges, Thiago V Seraphim, Paulo R Dores-Silva, Leandro R S Barbosa
Intrinsic flexibility is closely related to protein function, and a plethora of important regulatory proteins have been found to be flexible, multi-domain or even intrinsically disordered. On the one hand, understanding such systems depends on how these proteins behave in solution. On the other, small-angle X-ray scattering (SAXS) is a technique that fulfills the requirements to study protein structure and dynamics relatively quickly with few experimental limitations. Molecular chaperones from Hsp70 and Hsp90 families are multi-domain proteins containing flexible and/or disordered regions that play central roles in cellular proteostasis...
June 2016: Biophysical Reviews
https://www.readbyqxmd.com/read/28507559/the-dnaj-gene-family-in-pepper-capsicum-annuum-l-comprehensive-identification-characterization-and-expression-profiles
#5
FangFei Fan, Xian Yang, Yuan Cheng, Yunyan Kang, Xirong Chai
The DnaJ proteins which function as molecular chaperone played critical roles in plant growth and development and response to heat stress (HS) and also called heat shock protein 40 based on molecular weight. However, little was reported on this gene family in pepper. Recently, the release of the whole pepper genome provided an opportunity for identifying putative DnaJ homologous. In this study, a total of 76 putative pepper DnaJ genes (CaDnaJ01 to CaDnaJ76) were identified using bioinformatics methods and classified into five groups by the presence of the complete three domains (J-domain, zinc finger domain, and C-terminal domain)...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28506831/cryab-promotes-the-invasion-and-metastasis-of-colorectal-cancer-via-epithelial-mesenchymal-transition
#6
Chuanbing Shi, Xiaojun Yang, Xiaodong Bu, Ning Hou, Pingsheng Chen
Alpha B-crystallin (CRYAB, HSPB5) is a protein that was first discovered in the lens of the eye. It is a member of the small heat-shock protein family (sHsps). CRYAB functions primarily as a molecular chaperone to prevent the aggregation and degradation of damaged unfolded proteins due to cellular damage resulting from heat shock, radiation, oxidative stress, and other insults, thereby promoting cell survival and preventing apoptosis. In recent years, the role of CRYAB in tumorigenesis, tumor invasion, and metastasis has received increasing attention...
May 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28505454/perturbation-response-scanning-reveals-key-residues-for-allosteric-control-in-hsp70
#7
David Penkler, Ozge Sensoy, Canan Atilgan, Ozlem Tastan Bishop
Hsp70 molecular chaperones play an important role in maintaining cellular homeostasis, and are implicated in a wide array of cellular processes including protein recovery from aggregates, cross membrane protein translocation, and protein biogenesis. Hsp70 consists of two domains, a nucleotide binding domain (NBD) and a substrate binding domain (SBD), each of which communicates via an allosteric mechanism such that the protein interconverts between two functional states, an ATP bound open conformation and an ADP bound closed conformation...
May 15, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28504708/receptor-oligomerization-guides-pathway-choice-between-proteasomal-and-autophagic-degradation
#8
Kefeng Lu, Fabian den Brave, Stefan Jentsch
Abnormal or aggregated proteins have a strong cytotoxic potential and are causative for human disorders such as Alzheimer's, Parkinson's, Huntington's disease and amyotrophic lateral sclerosis. If not restored by molecular chaperones, abnormal proteins are typically degraded by proteasomes or eliminated by selective autophagy. The discovery that both pathways are initiated by substrate ubiquitylation but utilize different ubiquitin receptors incited a debate over how pathway choice is achieved. Here, we demonstrate in yeast that pathway choice is made after substrate ubiquitylation by competing ubiquitin receptors harbouring either proteasome- or autophagy-related protein 8 (Atg8/LC3)-binding modules...
May 15, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28501587/functional-requirements-for-djla-and-rraa-mediated-enhancement-of-recombinant-membrane-protein-production-in-the-engineered-escherichia-coli-strains-suptoxd-and-suptoxr
#9
Dimitra Gialama, Dafni Chrysanthi Delivoria, Myrsini Michou, Artemis Giannakopoulou, Georgios Skretas
In previous work, we have generated the engineered Escherichia coli strains SuptoxD and SuptoxR, which upon co-expression of the effector genes djlA or rraA, respectively, are capable of suppressing the cytotoxicity caused by membrane protein (MP) overexpression and producing dramatically enhanced yields for a variety of recombinant MPs of both prokaryotic and eukaryotic origin. Here, we investigated the functional requirements for DjlA- and RraA-mediated enhancement of recombinant MP production in these strains and show that: (i) DjlA and RraA act independently, i...
May 10, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28501017/golgi-independent-routes-support-protein-disulfide-isomerase-externalization-in-vascular-smooth-muscle-cells
#10
Thaís L S Araujo, Carolina G Fernandes, Francisco R M Laurindo
Extracellular pools of intracellular molecular chaperones are increasingly evident. The peri/epicellular(pec) pool of the endoplasmic reticulum redox chaperone protein disulfide isomerase-A1(PDI) is involved in thrombosis and vascular remodeling, while PDI externalization routes remain elusive. In endothelial cells, vesicular-type PDI secretion involves classical and unconventional pathways, while in platelets PDI exocytosis involves actin cytoskeleton. However, little is known about pecPDI in vascular smooth muscle cells(VSMC)...
May 3, 2017: Redox Biology
https://www.readbyqxmd.com/read/28500055/rnai-mediated-reverse-genetic-screen-identified-drosophila-chaperones-regulating-eye-and-neuromuscular-junction-morphology
#11
Sandeep Raut, Bhagaban Mallik, Arpan Parichha, Amrutha V, Chandan Sahi, Vimlesh Kumar
Accumulation of toxic proteins in neurons have been linked with the onset of neurodegenerative diseases, which in many cases, are characterized by altered neuronal function and synapse loss. Molecular chaperones help protein folding and resolubilization of unfolded proteins thereby reducing the protein aggregation stress. While most of the chaperones are expressed in neurons, their functional relevance largely remains unknown. Here, using bioinformatics analysis, we identified 95 Drosophila chaperones and classified them into seven different classes...
May 12, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28500030/translating-divergent-environmental-stresses-into-a-common-proteome-response-through-hik33-in-a-model-cyanobacterium
#12
Haitao Ge, Longfa Fang, Xiahe Huang, Jinlong Wang, Weiyang Chen, Ye Liu, Yuanya Zhang, Xiaorong Wang, Wu Xu, Qingfang He, Yingchun Wang
The histidine kinase Hik33 plays important roles in mediating cyanobacterial response to divergent types of abiotic stresses including cold, salt, high light (HL), and osmotic stresses. However, how these functions are regulated by Hik33 remains to be addressed. Using a hik33-deficient strain (Δhik33) of Synechocystis sp. PCC 6803 (Synechocystis) and quantitative proteomics, we found that Hik33 depletion induces differential protein expression highly similar to that induced by divergent types of stresses. This typically includes downregulation of proteins in photosynthesis and carbon assimilation that are necessary for cell propagation, and upregulation of heat shock proteins, chaperons, and proteases that are important for cell survival...
May 12, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28498401/luteolin-induced-apoptosis-through-activation-of-endoplasmic-reticulum-stress-sensors-in-pheochromocytoma-cells
#13
Kisang Kwon, Young-Sook Kwon, Seung-Whan Kim, Kweon Yu, Kyung-Ho Lee, O-Yu Kwon
Luteolin [2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-chromenone] is an active flavonoid compound from Lonicera japonica (Caprifoliaceae). Luteolin inhibits tumor cell proliferation, inflammatory and oxidative stress better, when compared with other flavonoids. In the present study, it was demonstrated that luteolin induces typical apoptosis in PC12 cells (derived from a pheochromocytoma of the rat adrenal medulla) accompanied by DNA fragmentation and formation of apoptotic bodies. In addition, luteolin regulates expression of the endoplasmic reticulum (ER) chaperone binding immunoglobulin protein, activating ER stress sensors (eukaryotic initiation factor 2α phosphorylation and X‑box binding protein 1 mRNA splicing) and induced autophagy...
May 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28498104/modeling-hsp70-hsp40-interaction-by-multi-scale-molecular-simulations-and-co-evolutionary-sequence-analysis
#14
Duccio Malinverni, Alfredo Jost Lopez, Paolo De Los Rios, Gerhard Hummer, Alessandro Barducci
The interaction between the Heat Shock Proteins 70 and 40 is at the core of the ATPase regulation of the chaperone machinery that maintains protein homeostasis. However, the structural details of the interaction are still elusive and contrasting models have been proposed for the transient Hsp70/Hsp40 complexes. Here we combine molecular simulations based on both coarse-grained and atomistic models with co-evolutionary sequence analysis to shed light on this problem by focusing on the bacterial DnaK/DnaJ system...
May 12, 2017: ELife
https://www.readbyqxmd.com/read/28497562/different-aggregation-states-of-a-nuclear-localization-signal-tagged-25-kda-c-terminal-fragment-of-tar-rna-dna-binding-protein-43%C3%A2-kda
#15
Akira Kitamura, Sachiko Yuno, Hideki Muto, Masataka Kinjo
The mechanism and cause of motor neuronal cell death in amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disorder, are unknown; gain of function of oligomers and aggregation of misfolded proteins, including carboxyl-terminal fragments (CTFs) of TAR RNA/DNA-binding protein 43 kDa (TDP-43), have been proposed as important causative factors in the onset of ALS. We recently reported that a nuclear localization signal (NLS)-tagged 25-kDa CTF of TDP-43 (TDP25) could decrease the cell-death proportion compared with that promoted by TDP25...
May 12, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28496363/prognostic-value-of-histone-chaperone-fact-subunits-expression-in-breast-cancer
#16
Kristopher Attwood, Daria Fleyshman, Laura Prendergast, Geraldine Paszkiewicz, Angela R Omilian, Wiam Bshara, Katerina Gurova
Understanding the underlying reasons for tumor aggressiveness, such as why some tumors grow slowly and locally, while others rapidly progress to a lethal metastatic disease, is still limited. This is especially critical in breast cancer (BrCa) due to its high prevalence and also due to the possibility that it can be detected early. Several oncogenes and tumor suppressors have been identified and are used in the prognosis and treatment of BrCa. However, even with these markers, the outcome within BrCa subtypes is highly variable...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28495962/dietary-supplementation-of-heat-treated-gracilaria-and-ulva-seaweeds-enhanced-acute-hypoxia-tolerance-in-gilthead-seabream-sparus-aurata
#17
Leonardo J Magnoni, Juan António Martos-Sitcha, Augusto Queiroz, Josep Alvar Calduch-Giner, José Fernando Magalhães Gonçalves, Cristina M R Rocha, Helena T Abreu, Johan W Schrama, Rodrigo O A Ozorio, Jaume Pérez-Sánchez
Intensive aquaculture practices involve rearing fish at high densities. In these conditions, fish may be exposed to suboptimal dissolved O2 levels with an increased formation of reactive O2 species (ROS) in tissues. Seaweeds (SW) contain biologically active substances with efficient antioxidant capacities. This study evaluated the effects of dietary supplementation of heat-treated SW (5% Gracilaria vermiculophylla or 5% Ulva lactuca) on stress bioindicators in seabream subjected to a hypoxic challenge. One hundred and sixty-eight fish (104...
May 11, 2017: Biology Open
https://www.readbyqxmd.com/read/28495886/the-sigma-1-receptor-modulates-dopamine-transporter-conformation-and-cocaine-binding-and-may-thereby-potentiate-cocaine-self-administration-in-rats
#18
Weimin Conrad Hong, Hideaki Yano, Takato Hiranita, Frederick T Chin, Christopher R McCurdy, Tsung-Ping Su, Susan G Amara, Jonathan L Katz
The dopamine transporter (DAT) regulates dopamine (DA) neurotransmission by recapturing DA into the presynaptic terminals, and is a principal target of the psychostimulant cocaine. The sigma-1 receptor (σ1R) is a molecular chaperone, and its ligands have been shown to modulate dopamine neuronal signaling, although their effects on DAT activity are unclear. Here, we report that the prototypical σ1R agonist (+)-pentazocine potentiated the dose response of cocaine self-administration in rats, consistent with effects of the σR agonists PRE-084 and DTG reported previously...
May 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28495509/cloning-of-three-heat-shock-protein-genes-hsp70-hsp90%C3%AE-and-hsp90%C3%AE-and-their-expressions-in-response-to-thermal-stress-in-loach-misgurnus-anguillicaudatus-fed-with-different-levels-of-vitamin-c
#19
Jie Yan, Xiao Liang, Yin Zhang, Yang Li, Xiaojuan Cao, Jian Gao
Heat shock protein 70 (HSP70) and 90 (HSP90) are the most broadly studied proteins in HSP families. They play key roles in cells as molecular chaperones, in response to stress conditions such as thermal stress. In this study, full-length cDNA sequences of HSP70, HSP90α and HSP90β from loach Misgurnus anguillicaudatus were cloned. The full-length cDNA of HSP70 in loach was 2332bp encoding 644 amino acids, while HSP90α and HSP90β were 2586bp and 2678bp in length, encoding 729 and 727 amino acids, respectively...
May 8, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28495207/targeting-the-hsp90-c-terminal-domain-to-induce-allosteric-inhibition-and-selective-client-downregulation
#20
Kourtney M Goode, Dino Petrov, Renee E Vickman, Scott A Crist, Pete E Pascuzzi, Tim L Ratliff, V Jo Davisson, Tony R Hazbun
BACKGROUND: Inhibition of Hsp90 is desirable due to potential downregulation of oncogenic clients. Early generation inhibitors bind to the N-terminal domain (NTD) but C-terminal domain (CTD) inhibitors are a promising class because they do not induce a heat shock response. Here we present a new structural class of CTD binding molecules with a unique allosteric inhibition mechanism. METHODS: A hit molecule, NSC145366, and structurally similar probes were assessed for inhibition of Hsp90 activities...
May 8, 2017: Biochimica et Biophysica Acta
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