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https://www.readbyqxmd.com/read/28716805/sensing-of-viral-and-endogenous-rna-by-zbp1-dai-induces-necroptosis
#1
Jonathan Maelfait, Layal Liverpool, Anne Bridgeman, Katherine B Ragan, Jason W Upton, Jan Rehwinkel
Nucleic acids are potent triggers for innate immunity. Double-stranded DNA and RNA adopt different helical conformations, including the unusual Z-conformation. Z-DNA/RNA is recognised by Z-binding domains (ZBDs), which are present in proteins implicated in antiviral immunity. These include ZBP1 (also known as DAI or DLM-1), which induces necroptosis, an inflammatory form of cell death. Using reconstitution and knock-in models, we report that mutation of key amino acids involved in Z-DNA/RNA binding in ZBP1's ZBDs prevented necroptosis upon infection with mouse cytomegalovirus...
July 17, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28707750/arterial-immune-protein-expression-demonstrates-the-complexity-of-immune-responses-in-kawasaki-disease-arteritis
#2
Scott A Cameron, Steven M White, David Arrollo, Stanford T Shulman, Anne H Rowley
BACKGROUND: A more complete understanding of immune-mediated damage to the coronary arteries in children with Kawasaki disease (KD) is required for improvements in patient treatment and outcomes. We recently reported the transcriptional profile of KD coronary arteritis, and here sought to determine protein expression of transcriptionally upregulated immune genes in KD coronary arteries from the first two months after disease onset. METHODS: We examined the coronary arteries of 12 fatal KD cases and 13 childhood controls for expression of a set of proteins whose genes were highly upregulated in the KD coronary artery transcriptome: allograft inflammatory factor 1 (AIF1), interleukin 18 (IL-18), CD74, CD1c, CD20 (MS4A1), Toll-like receptor 7 (TLR7), and Z-DNA binding protein 1 (ZBP1)...
July 14, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28695860/dna-conformational-transitions-inferred-from-re-evaluation-of-m-fo-d-fc-electron-density-maps
#3
Tomoko Sunami, Toshiyuki Chatake, Hidetoshi Kono
Conformational flexibility of DNA plays important roles in biological processes such as transcriptional regulation and DNA packaging etc. To understand the mechanisms of these processes, it is important to analyse when, where and how DNA shows conformational variations. Recent analyses have indicated that conventional refinement methods do not always provide accurate models of crystallographic heterogeneities and that some information on polymorphism has been overlooked in previous crystallographic studies...
July 1, 2017: Acta Crystallographica. Section D, Structural Biology
https://www.readbyqxmd.com/read/28652006/3d-nus-a-web-server-for-automated-modeling-and-visualization-of-non-canonical-3-dimensional-nucleic-acid-structures
#4
L Ponoop Prasad Patro, Abhishek Kumar, Narendar Kolimi, Thenmalarchelvi Rathinavelan
The inherent conformational flexibility of nucleic acids facilitate the formation of a range of conformations such as duplex, triplex, quadruplex etc. that play crucial roles in biological processes. Elucidation about the influence of non-canonical base pair mismatches on DNA/RNA structures at different sequence contexts to understand mismatch repair and misregulation of alternative splicing mechanisms as well as the sequence dependent effect of RNA-DNA hybrid in relevance to antisense strategy demand their three-dimensional structural information...
June 23, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28634194/zbp1-dai-ubiquitination-and-sensing-of-influenza-vrnps-activate-programmed-cell-death
#5
Sannula Kesavardhana, Teneema Kuriakose, Clifford S Guy, Parimal Samir, R K Subbarao Malireddi, Ashutosh Mishra, Thirumala-Devi Kanneganti
Innate sensing of influenza virus infection induces activation of programmed cell death pathways. We have recently identified Z-DNA-binding protein 1 (ZBP1) as an innate sensor of influenza A virus (IAV). ZBP1-mediated IAV sensing is critical for triggering programmed cell death in the infected lungs. Surprisingly, little is known about the mechanisms regulating ZBP1 activation to induce programmed cell death. Here, we report that the sensing of IAV RNA by retinoic acid inducible gene I (RIG-I) initiates ZBP1-mediated cell death via the RIG-I-MAVS-IFN-β signaling axis...
June 20, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28607035/murine-cytomegalovirus-ie3-dependent-transcription-is-required-for-dai-zbp1-mediated-necroptosis
#6
Haripriya Sridharan, Katherine B Ragan, Hongyan Guo, Ryan P Gilley, Vanessa J Landsteiner, William J Kaiser, Jason W Upton
DNA-dependent activator of interferon regulatory factors/Z-DNA binding protein 1 (DAI/ZBP1) is a crucial sensor of necroptotic cell death induced by murine cytomegalovirus (MCMV) in its natural host. Here, we show that viral capsid transport to the nucleus and subsequent viral IE3-dependent early transcription are required for necroptosis. Necroptosis induction does not depend on input virion DNA or newly synthesized viral DNA A putative RNA-binding domain of DAI/ZBP1, Zα2, is required to sense virus and trigger necroptosis...
June 12, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28602976/sting-signaling-in-tumorigenesis-and-cancer-therapy-a-friend-or-foe
#7
Liangmei He, Xiaomei Xiao, Xi Yang, Zixiang Zhang, Longhuo Wu, Zhiping Liu
Stimulator of interferon genes (STING) is a DNA sensor and an important cytoplasmic adaptor for other DNA sensors, such as Z-DNA binding protein 1 (DAI), DEAD-box helicase 41 (DDX41), and interferon-γ-inducible protein 16 (IFI16). The activation of STING signaling leads to the production of type I interferons and some other pro-inflammatory cytokines, which are critical for host defense against viral infection. Recent accumulating evidences suggest that STING is also involved in tumor development. However, the role of STING signaling in tumorigenesis is complicated, and a comprehensive review is still lacking...
June 7, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28594167/toward-an-expanded-genome-structural-and-computational-characterization-of-an-artificially-expanded-genetic-information-system
#8
Nigel G J Richards, Millie M Georgiadis
Although the fundamental properties of DNA as first proposed by Watson and Crick in 1953 provided a basic understanding of how duplex DNA was organized and might be replicated, it was not until the first crystal structures of DNA (Z-DNA in 1979, B-DNA in 1980, and A-DNA in 1982) that the true complexity of the molecule began to be appreciated. Many crystal structures of oligonucleotides have since shed light on the helical forms that "Watson-Crick" DNA can adopt, their associated groove widths, and the properties of the nucleobase pairs and their interactions in all three helical forms...
June 8, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28525806/a-novel-porphyrin-based-molecular-probe-zntcppspm4-with-catalytic-stabilizing-and-chiroptical-diagnostic-power-towards-dna-b-z-transition
#9
Chiara M A Gangemi, Alessandro D'Urso, Gaetano A Tomaselli, Nina Berova, Roberto Purrello
In this work we have designed a new zinc(II) porphyrin with four spermines conjugate in the meso positions, meso-tetrakis-(4-carboxysperminephenyl)porphyrin, ZnTCPPSpm4) with the aim of acting as a chiroptical probe for the Z-form of DNA, a high energy transient conformation of DNA. In addition to monitor by Electronic Circular Dichroism chiroptical response the formation of Z-DNA in the presence of micromolar concentration of spermine, this porphyrin based molecular probe is also able to catalyze and stabilize this important DNA structure...
May 14, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28506718/g-quadruplex-surveillance-in-bcl-2-gene-a-promising-therapeutic-intervention-in-cancer-treatment
#10
REVIEW
Pallabi Sengupta, Samit Chattopadhyay, Subhrangsu Chatterjee
BCL-2 overexpression promotes neoplastic cell expansion in cancers. Multiple noncanonical B-DNA motifs in the BCL-2 gene regulate selective modulation of its expression in normal and cancer cells. Three G-quadruplex topologies and one i-motif, in the vicinity of the P1 (major) promoter, stringently control its transcription. RNA quadruplexes and Z-DNA elements within translocation breakpoints of noncoding regions affect translation and promote oncogenic transformation of BCL-2 [e.g., t(14;18) translocation]...
May 12, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28498367/initiation-and-execution-mechanisms-of-necroptosis-an-overview
#11
REVIEW
Sasker Grootjans, Tom Vanden Berghe, Peter Vandenabeele
Necroptosis is a form of regulated cell death, which is induced by ligand binding to TNF family death domain receptors, pattern recognizing receptors and virus sensors. The common feature of these receptor systems is the implication of proteins, which contain a receptor interaction protein kinase (RIPK) homology interaction motif (RHIM) mediating recruitment and activation of receptor-interacting protein kinase 3 (RIPK3), which ultimately activates the necroptosis executioner mixed lineage kinase domain-like (MLKL)...
May 12, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28399366/polarizable-force-field-for-dna-based-on-the-classical-drude-oscillator-i-refinement-using-quantum-mechanical-base-stacking-and-conformational-energetics
#12
Justin A Lemkul, Alexander D MacKerell
Empirical force fields seek to relate the configuration of a set of atoms to its energy, thus yielding the forces governing its dynamics, using classical physics rather than more expensive quantum mechanical calculations that are computationally intractable for large systems. Most force fields used to simulate biomolecular systems use fixed atomic partial charges, neglecting the influence of electronic polarization, instead making use of a mean-field approximation that may not be transferable across environments...
May 9, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28398748/polarizable-force-field-for-dna-based-on-the-classical-drude-oscillator-ii-microsecond-molecular-dynamics-simulations-of-duplex-dna
#13
Justin A Lemkul, Alexander D MacKerell
The structure and dynamics of DNA are governed by a sensitive balance between base stacking and pairing, hydration, and interactions with ions. Force-field models that include explicit representations of electronic polarization are capable of more accurately modeling the subtle details of these interactions versus commonly used additive force fields. In this work, we validate our recently refined polarizable force field for DNA based on the classical Drude oscillator model, in which electronic degrees of freedom are represented as negatively charged particles attached to their parent atoms via harmonic springs...
May 9, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28398495/a-histological-study-of-fulminant-type-1-diabetes-mellitus-related-to-human-cytomegalovirus-reactivation
#14
Sho Yoneda, Akihisa Imagawa, Kenji Fukui, Sae Uno, Junji Kozawa, Makoto Sakai, Toshiki Yumioka, Hiromi Iwahashi, Iichiro Shimomura
Context: Fulminant type 1 diabetes mellitus (T1DM) is thought to be partly caused by virus infection. Objective: This study investigated the mechanism of β cell destruction in fulminant T1DM after drug-induced hypersensitivity syndrome (DIHS). Methods: We determined the localization of viruses of human cytomegalovirus (HCMV), human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV), and the expression of interferon regulatory factor 3 (IRF3) and viral receptors of Z DNA binding protein 1 (ZBP1) and retinoic acid-inducible gene I (RIG-I), together with inflammatory cells by immunohistochemistry of pancreas from an autopsy fulminant T1DM patient with DIHS or seven subjects with normal glucose tolerance who underwent pancreatectomy...
April 10, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27943481/synchronized-chiral-induction-between-5-helicene-spermine-ligand-and-b-z-dna-transition
#15
Kensuke Kawara, Genichiro Tsuji, Yosuke Taniguchi, Shigeki Sasaki
The 2,13-dimethoxy[5]helicene-spermine ligand 8 b possesses an axial chirality. The racemic 8 b was bound to B-DNA by the accompanying induction of its (P)-chirality together with the B-to-Z helicity change of the duplex DNA, [(dC-dG)3 ]2 . The (P)-chirality of the bound 8 b, in turn, transitioned to the (M)-chirality according to the Z-helicity of the DNA. These results illustrate the chirality synchronization between the DNA and the ligand.
December 11, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27942647/probing-helical-transitions-in-a-dna-duplex
#16
Debayan Chakraborty, David J Wales
The complex conformational change from B-DNA to Z-DNA requires inversion of helix-handedness. Multiple degrees of freedom are intricately coupled during this transition, and formulating an appropriate reaction coordinate that captures the underlying complexity would be problematic. In this contribution, we adopt an alternative approach, based on the potential energy landscape perspective, to construct a kinetic transition network. Microscopic insight into the B → Z transition is provided in terms of geometrically defined discrete paths consisting of local minima and the transition states that connect them...
December 21, 2016: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/27917412/zbp1-dai-is-an-innate-sensor-of-influenza-virus-triggering-the-nlrp3-inflammasome-and-programmed-cell-death-pathways
#17
Teneema Kuriakose, Si Ming Man, R K Subbarao Malireddi, Rajendra Karki, Sannula Kesavardhana, David E Place, Geoffrey Neale, Peter Vogel, Thirumala-Devi Kanneganti
The interferon-inducible protein Z-DNA binding protein 1 (ZBP1, also known as DNA-dependent activator of IFN-regulatory factors (DAI) and DLM-1) was identified as a dsDNA sensor, which instigates innate immune responses. However, this classification has been disputed and whether ZBP1 functions as a pathogen sensor during an infection has remained unknown. Herein, we demonstrated ZBP1-mediated sensing of the influenza A virus (IAV) proteins NP and PB1, triggering cell death and inflammatory responses via the RIPK1-RIPK3-Caspase-8 axis...
August 5, 2016: Science Immunology
https://www.readbyqxmd.com/read/27900812/spontaneous-assembly-of-an-organic-inorganic-nucleic-acid-z-dna-double-helix-structure
#18
Vladislav Kulikov, Naomi A B Johnson, Andrew J Surman, Marie Hutin, Sharon M Kelly, Mohammed Hezwani, De-Liang Long, Gerd Meyer, Leroy Cronin
Herein, we report a hybrid polyoxometalate organic-inorganic compound, Na2 [(HGMP)2 Mo5 O15 ]⋅7 H2 O (1; where GMP=guanosine monophosphate), which spontaneously assembles into a structure with dimensions that are strikingly similar to those of the naturally occurring left-handed Z-form of DNA. The helical parameters in the crystal structure of the new compound, such as rise per turn and helical twist per dimer, are nearly identical to this DNA conformation, allowing a close comparison of the two structures...
November 30, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27890616/cerium-chloride-stimulated-controlled-conversion-of-b-to-z-dna-in-self-assembled-nanostructures
#19
Madhabi M Bhanjadeo, Ashok K Nayak, Umakanta Subudhi
DNA adopts different conformation not only because of novel base pairs but also while interacting with inorganic or organic compounds. Self-assembled branched DNA (bDNA) structures or DNA origami that change conformation in response to environmental cues hold great promises in sensing and actuation at the nanoscale. Recently, the B-Z transition in DNA is being explored to design various nanomechanical devices. In this communication we have demonstrated that Cerium chloride binds to the phosphate backbone of self-assembled bDNA structure and induce B-to-Z transition at physiological concentration...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27856245/nmr-elucidation-of-reduced-b-z-transition-activity-of-pkz-protein-kinase-at-high-nacl-concentration
#20
Ae-Ree Lee, Yeo-Jin Seo, Seo-Ree Choi, Kyoung-Seok Ryu, Hae-Kap Cheong, Shim Sung Lee, Masato Katahira, Chin-Ju Park, Joon-Hwa Lee
A Z-DNA binding protein (ZBP)-containing protein kinase (PKZ) in fish species has an important role in the innate immune response. Previous structural studies of the Zα domain of the PKZ from Carassius auratus (caZαPKZ) showed that the protein initially binds to B-DNA and induces B-Z transition of double stranded DNA in a salt concentration-dependent manner. However, the significantly reduced B-Z transition activity of caZαPKZ at high salt concentration was not fully understood. In this study, we present the binding affinity of the protein for B-DNA and Z-DNA and characterize its extremely low B-Z transition activity at 250 mM NaCl...
January 8, 2017: Biochemical and Biophysical Research Communications
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