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https://www.readbyqxmd.com/read/28636937/the-conserved-rna-binding-cyclophilin-rct1-regulates-small-rna-biogenesis-and-splicing-independent-of-heterochromatin-assembly
#1
An-Yun Chang, Stephane E Castel, Evan Ernst, Hyun Soo Kim, Robert A Martienssen
RNAi factors and their catalytic activities are essential for heterochromatin assembly in S. pombe. This has led to the idea that siRNAs can promote H3K9 methylation by recruiting the cryptic loci regulator complex (CLRC), also known as recombination in K complex (RIKC), to the nucleation site. The conserved RNA-binding protein Rct1 (AtCyp59/SIG-7) interacts with splicing factors and RNA polymerase II. Here we show that Rct1 promotes processing of pericentromeric transcripts into siRNAs via the RNA recognition motif...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28623276/gag-protease-coevolution-analyses-define-novel-structural-surfaces-in-the-hiv-1-matrix-and-capsid-involved-in-resistance-to-protease-inhibitors
#2
Francisco M Codoñer, Ruth Peña, Oscar Blanch-Lombarte, Esther Jimenez-Moyano, Maria Pino, Thomas Vollbrecht, Bonaventura Clotet, Javier Martinez-Picado, Rika Draenert, Julia G Prado
Despite the major role of Gag in establishing resistance of HIV-1 to protease inhibitors (PIs), very limited data are available on the total contribution of Gag residues to resistance to PIs. To identify in detail Gag residues and structural interfaces associated with the development of HIV-1 resistance to PIs, we traced viral evolution under the pressure of PIs using Gag-protease single genome sequencing and coevolution analysis of protein sequences in 4 patients treated with PIs over a 9-year period. We identified a total of 38 Gag residues correlated with the protease, 32 of which were outside Gag cleavage sites...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28619996/farnesoid-x-receptor-and-liver-x-receptor-ligands-initiate-formation-of-coated-platelets
#3
Amanda J Unsworth, Alexander P Bye, Dionne S Tannetta, Michael J R Desborough, Neline Kriek, Tanya Sage, Harriet E Allan, Marilena Crescente, Parveen Yaqoob, Timothy D Warner, Chris I Jones, Jonathan M Gibbins
OBJECTIVES: The liver X receptors (LXRs) and farnesoid X receptor (FXR) have been identified in human platelets. Ligands of these receptors have been shown to have nongenomic inhibitory effects on platelet activation by platelet agonists. This, however, seems contradictory with the platelet hyper-reactivity that is associated with several pathological conditions that are associated with increased circulating levels of molecules that are LXR and FXR ligands, such as hyperlipidemia, type 2 diabetes mellitus, and obesity...
June 15, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28619100/cyclophilin-b-facilitates-the-replication-of-orf-virus
#4
Kui Zhao, Jida Li, Wenqi He, Deguang Song, Ximu Zhang, Di Zhang, Yanlong Zhou, Feng Gao
BACKGROUND: Viruses interact with host cellular factors to construct a more favourable environment for their efficient replication. Expression of cyclophilin B (CypB), a cellular peptidyl-prolyl cis-trans isomerase (PPIase), was found to be significantly up-regulated. Recently, a number of studies have shown that CypB is important in the replication of several viruses, including Japanese encephalitis virus (JEV), hepatitis C virus (HCV) and human papillomavirus type 16 (HPV 16). However, the function of cellular CypB in ORFV replication has not yet been explored...
June 15, 2017: Virology Journal
https://www.readbyqxmd.com/read/28597937/frustration-guided-motion-planning-reveals-conformational-transitions-in-proteins
#5
Dominik Budday, Rasmus Fonseca, Sigrid Leyendecker, Henry van den Bedem
Proteins exist as conformational ensembles, exchanging between substates to perform their function. Advances in experimental techniques yield unprecedented access to structural snapshots of their conformational landscape. However, computationally modeling how proteins use collective motions to transition between substates is challenging owing to a rugged landscape and large energy barriers. Here, we present a new, robotics-inspired motion planning procedure called dCC-RRT that navigates the rugged landscape between substates by introducing dynamic, interatomic constraints to modulate frustration...
June 9, 2017: Proteins
https://www.readbyqxmd.com/read/28594325/cyclophilin-a-regulated-ubiquitination-is-critical-for-rig-i-mediated-antiviral-immune-responses
#6
Wei Liu, Jing Li, Weinan Zheng, Yingli Shang, Zhendong Zhao, Shanshan Wang, Yuhai Bi, Shuang Zhang, Chongfeng Xu, Ziyuan Duan, Lianfeng Zhang, Yue Lynn Wang, Zhengfan Jiang, Wenjun Liu, Lei Sun
RIG-I is a key cytosolic pattern recognition receptor that interacts with MAVS to induce type I interferons (IFNs) against RNA virus infection. In this study, we found that cyclophilin A (CypA), a peptidyl-prolyl cis/trans isomerase, functioned as a critical positive regulator of RIG-I-mediated antiviral immune responses. Deficiency of CypA impaired RIG-I-mediated type I IFN production and promoted viral replication in human cells and mice. Upon Sendai virus infection, CypA increased the interaction between RIG-I and its E3 ubiquitin ligase TRIM25, leading to enhanced TRIM25-mediated K63-linked ubiquitination of RIG-I that facilitated recruitment of RIG-I to MAVS...
June 8, 2017: ELife
https://www.readbyqxmd.com/read/28591721/ginkgolide-k-attenuates-neuronal-injury-after-ischemic-stroke-by-inhibiting-mitochondrial-fission-and-gsk-3%C3%AE-dependent-increases-in-mitochondrial-membrane-permeability
#7
Xu Zhou, Hui-Ying Wang, Bin Wu, Cai-Yi Cheng, Wei Xiao, Zhen-Zhong Wang, Yu-Yu Yang, Ping Li, Hua Yang
Ginkgolide K (GK) belongs to the ginkgolide family of natural compounds found in Ginkgo biloba leaves, which have been used for centuries to treat cerebrovascular and cardiovascular diseases. We evaluated the protective effects of GK against neuronal apoptosis by assessing its ability to sustain mitochondrial integrity and function. Co-immunoprecipitation showed that Drp1 binding to GSK-3β was increased after an oxygen-glucose deprivation/reperfusion (OGD/R) insult in cultured neuroblastoma cells. This induced Drp1 and GSK-3β translocation to mitochondria and mitochondrial dysfunction, which was attenuated by GK...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28584448/identification-and-characterization-of-a-cyclosporin-binding-cyclophilin-from-staphylococcus-aureus-newman
#8
Soumitra Polley, Soham Seal, Avisek Mahapa, Biswanath Jana, Anindya Biswas, Sukhendu Mandal, Debabrata Sinha, Keya Sau, Subrata Sau
Cyclophilins, a class of peptidyl-prolyl cis-trans isomerase (PPIase) enzymes, are inhibited by cyclosporin A (CsA), an immunosuppressive drug. Staphylococcus aureus Newman, a pathogenic bacterium, carries a gene for encoding a putative cyclophilin (SaCyp). SaCyp shows significant homology with other cyclophilins at the sequence level. A three-dimensional model structure of SaCyp harbors a binding site for CsA. To verify whether SaCyp possesses both the PPIase activity and the CsA binding ability, we have purified and investigated a recombinant SaCyp (rCyp) using various in vitro tools...
2017: Bioinformation
https://www.readbyqxmd.com/read/28580168/caml-mediates-survival-of-myc-induced-lymphoma-cells-independent-of-tail-anchored-protein-insertion
#9
Jennifer C Shing, Lonn D Lindquist, Nica Borgese, Richard J Bram
Calcium-modulating cyclophilin ligand (CAML) is an endoplasmic reticulum (ER) protein that functions, along with WRB and TRC40, to mediate tail-anchored (TA) protein insertion into the ER membrane. Physiologic roles for CAML include endocytic trafficking, intracellular calcium signaling, and the survival and proliferation of specialized immune cells, recently attributed to its requirement for TA protein insertion. To identify a possible role for CAML in cancer cells, we generated Eμ-Myc transgenic mice that carry a tamoxifen-inducible deletion allele of Caml...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28569216/potent-and-reversible-lentiviral-vector-restriction-in-murine-induced-pluripotent-stem-cells
#10
Franziska K Geis, Melanie Galla, Dirk Hoffmann, Johannes Kuehle, Daniela Zychlinski, Tobias Maetzig, Juliane W Schott, Adrian Schwarzer, Christine Goffinet, Stephen P Goff, Axel Schambach
BACKGROUND: Retroviral vectors are derived from wild-type retroviruses, can be used to study retrovirus-host interactions and are effective tools in gene and cell therapy. However, numerous cell types are resistant or less permissive to retrovirus infection due to the presence of active defense mechanisms, or the absence of important cellular host co-factors. In contrast to multipotent stem cells, pluripotent stem cells (PSC) have potential to differentiate into all three germ layers...
May 31, 2017: Retrovirology
https://www.readbyqxmd.com/read/28567569/on-the-role-ecology-phylogeny-and-structure-of-dual-family-immunophilins
#11
Sailen Barik
The novel class of dual-family immunophilins (henceforth abbreviated as DFI) represents naturally occurring chimera of classical FK506-binding protein (FKBP) and cyclophilin (CYN), connected by a flexible linker that may include a three-unit tetratricopeptide (TPR) repeat. Here, I report a comprehensive analysis of all current DFI sequences and their host organisms. DFIs are of two kinds: CFBP (cyclosporin- and FK506-binding protein) and FCBP (FK506- and cyclosporin-binding protein), found in eukaryotes. The CFBP type occurs in select bacteria that are mostly extremophiles, such as psychrophilic, thermophilic, halophilic, and sulfur-reducing...
May 31, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28566382/human-papillomavirus-major-capsid-protein-l1-remains-associated-with-the-incoming-viral-genome-throughout-the-entry-process
#12
Stephen DiGiuseppe, Malgorzata Bienkowska-Haba, Lucile G M Guion, Timothy R Keiffer, Martin Sapp
During infectious entry, acidification within the endosome triggers uncoating of the HPV capsid whereupon host cyclophilins facilitate the release of most of the major capsid protein, L1, from the minor capsid protein L2 and the viral genome. The L2/DNA complex traffics to the trans-Golgi network (TGN). Following the onset of mitosis, HPV-harboring transport vesicles bud from the TGN followed by association with mitotic chromosomes. During this time, the HPV genome remains in a vesicular compartment until the nucleus has completely reformed...
May 31, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28562665/correction-a-conserved-nuclear-cyclophilin-is-required-for-both-rna-polymerase-ii-elongation-and-co-transcriptional-splicing-in-caenorhabditis-elegans
#13
Jeong H Ahn, Andreas Rechtsteiner, Susan Strome, William G Kelly
[This corrects the article DOI: 10.1371/journal.pgen.1006227.].
May 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28559847/high-sensitivity-of-sirt3-deficient-hearts-to-ischemia-reperfusion-is-associated-with-mitochondrial-abnormalities
#14
Rebecca M Parodi-Rullán, Xavier Chapa-Dubocq, Pedro J Rullán, Sehwan Jang, Sabzali Javadov
Aim: Sirtuins are NAD(+)-dependent deacetylases that regulate cell metabolism through protein acetylation/deacetylation, and SIRT3 is the major deacetylase among mitochondrial isoforms. Here, we elucidated the possible role of acetylation of cyclophilin D, a key regulator of the mitochondrial permeability transition pore (mPTP), in mitochondria-mediated cardiac dysfunction induced by ischemia-reperfusion (IR) in wild type (WT) and SIRT3 knockout (SIRT3(-/-)) mice. Materials and Methods: Isolated and Langendorff-mode perfused hearts of WT and SIRT3(-/-) mice were subjected to 25-min global ischemia followed by 60-min of reperfusion in the presence or absence of the mPTP inhibitor, sanglifehrin A (SfA)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28552321/vital-role-for-cyclophilin-b-cypb-in-asexual-development-dimorphic-transition-and-virulence-of-beauveria-bassiana
#15
Zhen-Jian Chu, Huan-Huan Sun, Sheng-Hua Ying, Ming-Guang Feng
Cyclophilin B (CypB) was previously revealed as one of many putative secretory proteins in the transcriptome of Beauveria bassiana infection to a lepidopteran pest. Here we show a main localization of CypB in hyphal cell walls and septa and its essential role in the in vitro and in vivo asexual cycles of the fungal insect pathogen. Deletion of cypB reduced colony growth by 16-42% on two rich media and 30 scant media with different carbon or nitrogen sources. The deletion mutant suffered a delayed conidiation on a standard medium and a final 47% reduction in conidial yield, accompanied with drastic transcript depression of several key genes required for conidiation and conidial maturation...
May 25, 2017: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/28539497/correction-to-extracellular-cyclophilin-a-especially-acetylated-causes-pulmonary-hypertension-by-stimulating-endothelial-apoptosis-redox-stress-and-inflammation
#16
(no author information available yet)
No abstract text is available yet for this article.
June 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28535337/overall-structural-model-of-ns5a-protein-from-hepatitis-c-virus-and-modulation-by-mutations-confering-resistance-of-virus-replication-to-cyclosporin-a
#17
Aurelie Badillo, Véronique Receveur-Brechot, Stéphane Sarrazin, François-Xavier Cantrelle, Frédéric Delolme, Marie-Laure Fogeron, Jennifer Molle, Roland Montserret, Anja Bockmann, Ralf Bartenschlager, Volker Lohmann, Guy Lippens, Sylvie Ricard-Blum, Xavier Hanoulle, François Penin
Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a RNA-binding phosphoprotein composed of a N-terminal membrane anchor (AH), a structured domain 1 (D1), and two intrinsically disordered domains (D2 and D3). The knowledge of the functional architecture of this multifunctional protein remains limited. We report here that NS5A-D1D2D3 produced in a wheat germ cell-free system is obtained under a highly phosphorylated state. Its NMR analysis revealed that these phosphorylations do not change the disordered nature of D2 and D3 domains but increase the number of conformers due to partial phosphorylations...
June 7, 2017: Biochemistry
https://www.readbyqxmd.com/read/28518150/cycloheximide-promotes-paraptosis-induced-by-inhibition-of-cyclophilins-in-glioblastoma-multiforme
#18
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/28506462/a-slow-conformational-switch-in-the-bmal1-transactivation-domain-modulates-circadian-rhythms
#19
Chelsea L Gustafson, Nicole C Parsley, Hande Asimgil, Hsiau-Wei Lee, Christopher Ahlbach, Alicia K Michael, Haiyan Xu, Owen L Williams, Tara L Davis, Andrew C Liu, Carrie L Partch
The C-terminal transactivation domain (TAD) of BMAL1 (brain and muscle ARNT-like 1) is a regulatory hub for transcriptional coactivators and repressors that compete for binding and, consequently, contributes to period determination of the mammalian circadian clock. Here, we report the discovery of two distinct conformational states that slowly exchange within the dynamic TAD to control timing. This binary switch results from cis/trans isomerization about a highly conserved Trp-Pro imide bond in a region of the TAD that is required for normal circadian timekeeping...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28501872/a-mechanism-study-underlying-the-protective-effects-of-cyclosporine-a-on-lung-ischemia-reperfusion-injury
#20
Jian''an Li, Zhongya Yan, Qianjin Fang
AIM: This study is aimed at validating the hypothesis that administration of cyclosporine-A (CsA) would be protective in lung ischemia-reperfusion (I/R) injury and in exploring the underlying mechanism. METHODS: Rabbits were divided into 4 groups: the control, sham operation, I/R, and I/R with CsA treatment. Flow cytometry was used to measure the mitochondrial membrane potential. Laser scanning confocal microscope was used to analyze mitochondrion permeability transition pore (MPTP)...
2017: Pharmacology
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