Articles de revues : « Macrodomains »

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Haikarainen, Teemu, Mirko M. Maksimainen, Ezeogo Obaji et Lari Lehtiö. « Development of an Inhibitor Screening Assay for Mono-ADP-Ribosyl Hydrolyzing Macrodomains Using AlphaScreen Technology ». SLAS DISCOVERY : Advancing the Science of Drug Discovery 23, n^o 3 (13 octobre 2017) : 255–63. http://dx.doi.org/10.1177/2472555217737006.

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Protein mono-ADP-ribosylation is a posttranslational modification involved in the regulation of several cellular signaling pathways. Cellular ADP-ribosylation is regulated by ADP-ribose hydrolases via a hydrolysis of the protein-linked ADP-ribose. Most of the ADP-ribose hydrolases share a macrodomain fold. Macrodomains have been linked to several diseases, such as cancer, but their cellular roles are mostly unknown. Currently, there are no inhibitors available targeting the mono-ADP-ribose hydrolyzing macrodomains. We have developed a robust AlphaScreen assay for the screening of inhibitors against macrodomains having mono-ADP-ribose hydrolysis activity. We utilized this assay for validatory screening against human MacroD1 and identified five compounds inhibiting the macrodomain. Dose–response measurements and an orthogonal assay further validated four of these compounds as MacroD1 inhibitors. The developed assay is homogenous, easy to execute, and suitable for the screening of large compound libraries. The assay principle can also be adapted for other ADP-ribose hydrolyzing macrodomains, which can utilize a biotin-mono-ADP-ribosylated protein as a substrate.

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Hammond, Robert G., Norbert Schormann, Robert Lyle McPherson, Anthony K. L. Leung, Champion C. S. Deivanayagam et Margaret A. Johnson. « ADP-ribose and analogues bound to the deMARylating macrodomain from the bat coronavirus HKU4 ». Proceedings of the National Academy of Sciences 118, n^o 2 (4 janvier 2021) : e2004500118. http://dx.doi.org/10.1073/pnas.2004500118.

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Macrodomains are proteins that recognize and hydrolyze ADP ribose (ADPR) modifications of intracellular proteins. Macrodomains are implicated in viral genome replication and interference with host cell immune responses. They are important to the infectious cycle of Coronaviridae and Togaviridae viruses. We describe crystal structures of the conserved macrodomain from the bat coronavirus (CoV) HKU4 in complex with ligands. The structures reveal a binding cavity that accommodates ADPR and analogs via local structural changes within the pocket. Using a radioactive assay, we present evidence of mono-ADPR (MAR) hydrolase activity. In silico analysis presents further evidence on recognition of the ADPR modification for hydrolysis. Mutational analysis of residues within the binding pocket resulted in diminished enzymatic activity and binding affinity. We conclude that the common structural features observed in the macrodomain in a bat CoV contribute to a conserved function that can be extended to other known macrodomains.

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Rack, Johannes Gregor Matthias, Valentina Zorzini, Zihan Zhu, Marion Schuller, Dragana Ahel et Ivan Ahel. « Viral macrodomains : a structural and evolutionary assessment of the pharmacological potential ». Open Biology 10, n^o 11 (novembre 2020) : 200237. http://dx.doi.org/10.1098/rsob.200237.

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Viral macrodomains possess the ability to counteract host ADP-ribosylation, a post-translational modification implicated in the creation of an antiviral environment via immune response regulation. This brought them into focus as promising therapeutic targets, albeit the close homology to some of the human macrodomains raised concerns regarding potential cross-reactivity and adverse effects for the host. Here, we evaluate the structure and function of the macrodomain of SARS-CoV-2, the causative agent of COVID-19. We show that it can antagonize ADP-ribosylation by PARP14, a cellular (ADP-ribosyl)transferase necessary for the restriction of coronaviral infections. Furthermore, our structural studies together with ligand modelling revealed the structural basis for poly(ADP-ribose) binding and hydrolysis, an emerging new aspect of viral macrodomain biology. These new insights were used in an extensive evolutionary analysis aimed at evaluating the druggability of viral macrodomains not only from the Coronaviridae but also Togaviridae and Iridoviridae genera (causing diseases such as Chikungunya and infectious spleen and kidney necrosis virus disease, respectively). We found that they contain conserved features, distinct from their human counterparts, which may be exploited during drug design.

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Ekblad, Torun, Patricia Verheugd, Anders E. Lindgren, Tomas Nyman, Mikael Elofsson et Herwig Schüler. « Identification of Poly(ADP-Ribose) Polymerase Macrodomain Inhibitors Using an AlphaScreen Protocol ». SLAS DISCOVERY : Advancing the Science of Drug Discovery 23, n^o 4 (9 janvier 2018) : 353–62. http://dx.doi.org/10.1177/2472555217750870.

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Macrodomains recognize intracellular adenosine diphosphate (ADP)-ribosylation resulting in either removal of the modification or a protein interaction event. Research into compounds that modulate macrodomain functions could make important contributions. We investigated the interactions of all seven individual macrodomains of the human poly(ADP-ribose) polymerase (PARP) family members PARP9, PARP14, and PARP15 with five mono-ADP-ribosylated (automodified) ADP-ribosyltransferase domains using an AlphaScreen assay. Several mono-ADP-ribosylation-dependent interactions were identified, and they were found to be in the micromolar affinity range using surface plasmon resonance (SPR). We then focused on the interaction between PARP14 macrodomain-2 and the mono-ADP-ribosylated PARP10 catalytic domain, and probed a ~1500-compound diverse library for inhibitors of this interaction using AlphaScreen. Initial hit compounds were verified by concentration–response experiments using AlphaScreen and SPR, and they were tested against PARP14 macrodomain-2 and -3. Two initial hit compounds and one chemical analog each were further characterized using SPR and microscale thermophoresis. In conclusion, our results reveal novel macrodomain interactions and establish protocols for identification of inhibitors of such interactions.

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Kuri, Thomas, Klara K. Eriksson, Akos Putics, Roland Züst, Eric J. Snijder, Andrew D. Davidson, Stuart G. Siddell, Volker Thiel, John Ziebuhr et Friedemann Weber. « The ADP-ribose-1″-monophosphatase domains of severe acute respiratory syndrome coronavirus and human coronavirus 229E mediate resistance to antiviral interferon responses ». Journal of General Virology 92, n^o 8 (1 août 2011) : 1899–905. http://dx.doi.org/10.1099/vir.0.031856-0.

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Several plus-strand RNA viruses encode proteins containing macrodomains. These domains possess ADP-ribose-1″-phosphatase (ADRP) activity and/or bind poly(ADP-ribose), poly(A) or poly(G). The relevance of these activities in the viral life cycle has not yet been resolved. Here, we report that genetically engineered mutants of severe acute respiratory syndrome coronavirus (SARS-CoV) and human coronavirus 229E (HCoV-229E) expressing ADRP-deficient macrodomains displayed an increased sensitivity to the antiviral effect of alpha interferon compared with their wild-type counterparts. The data suggest that macrodomain-associated ADRP activities may have a role in viral escape from the innate immune responses of the host.

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Hussain, Irfan, Nashaiman Pervaiz, Abbas Khan, Shoaib Saleem, Huma Shireen, Dong-Qing Wei, Viviane Labrie, Yiming Bao et Amir Ali Abbasi. « Evolutionary and structural analysis of SARS-CoV-2 specific evasion of host immunity ». Genes & ; Immunity 21, n^o 6-8 (décembre 2020) : 409–19. http://dx.doi.org/10.1038/s41435-020-00120-6.

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AbstractThe outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading fast worldwide. There is a pressing need to understand how the virus counteracts host innate immune responses. Deleterious clinical manifestations of coronaviruses have been associated with virus-induced direct dysregulation of innate immune responses occurring via viral macrodomains located within nonstructural protein-3 (Nsp3). However, no substantial information is available concerning the relationship of macrodomains to the unusually high pathogenicity of SARS-CoV-2. Here, we show that structural evolution of macrodomains may impart a critical role to the unique pathogenicity of SARS-CoV-2. Using sequence, structural, and phylogenetic analysis, we identify a specific set of historical substitutions that recapitulate the evolution of the macrodomains that counteract host immune response. These evolutionary substitutions may alter and reposition the secondary structural elements to create new intra-protein contacts and, thereby, may enhance the ability of SARS-CoV-2 to inhibit host immunity. Further, we find that the unusual virulence of this virus is potentially the consequence of Darwinian selection‐driven epistasis in protein evolution. Our findings warrant further characterization of macrodomain-specific evolutionary substitutions in in vitro and in vivo models to determine their inhibitory effects on the host immune system.

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Leung, Anthony K. L., Diane E. Griffin, Jürgen Bosch et Anthony R. Fehr. « The Conserved Macrodomain Is a Potential Therapeutic Target for Coronaviruses and Alphaviruses ». Pathogens 11, n^o 1 (14 janvier 2022) : 94. http://dx.doi.org/10.3390/pathogens11010094.

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Emerging and re-emerging viral diseases pose continuous public health threats, and effective control requires a combination of non-pharmacologic interventions, treatment with antivirals, and prevention with vaccines. The COVID-19 pandemic has demonstrated that the world was least prepared to provide effective treatments. This lack of preparedness has been due, in large part, to a lack of investment in developing a diverse portfolio of antiviral agents, particularly those ready to combat viruses of pandemic potential. Here, we focus on a drug target called macrodomain that is critical for the replication and pathogenesis of alphaviruses and coronaviruses. Some mutations in alphavirus and coronaviral macrodomains are not tolerated for virus replication. In addition, the coronavirus macrodomain suppresses host interferon responses. Therefore, macrodomain inhibitors have the potential to block virus replication and restore the host’s protective interferon response. Viral macrodomains offer an attractive antiviral target for developing direct acting antivirals because they are highly conserved and have a structurally well-defined (druggable) binding pocket. Given that this target is distinct from the existing RNA polymerase and protease targets, a macrodomain inhibitor may complement current approaches, pre-empt the threat of resistance and offer opportunities to develop combination therapies for combating COVID-19 and future viral threats.

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Zapata-Pérez, Rubén, Fernando Gil-Ortiz, Ana Belén Martínez-Moñino, Antonio Ginés García-Saura, Jordi Juanhuix et Álvaro Sánchez-Ferrer. « Structural and functional analysis of Oceanobacillus iheyensis macrodomain reveals a network of waters involved in substrate binding and catalysis ». Open Biology 7, n^o 4 (avril 2017) : 160327. http://dx.doi.org/10.1098/rsob.160327.

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Macrodomains are ubiquitous conserved domains that bind or transform ADP-ribose (ADPr) metabolites. In humans, they are involved in transcription, X-chromosome inactivation, neurodegeneration and modulating PARP1 signalling, making them potential targets for therapeutic agents. Unfortunately, some aspects related to the substrate binding and catalysis of MacroD-like macrodomains still remain unclear, since mutation of the proposed catalytic aspartate does not completely abolish enzyme activity. Here, we present a functional and structural characterization of a macrodomain from the extremely halotolerant and alkaliphilic bacterium Oceanobacillus iheyensis (OiMacroD), related to hMacroD1/hMacroD2, shedding light on substrate binding and catalysis. The crystal structures of D40A, N30A and G37V mutants, and those with MES, ADPr and ADP bound, allowed us to identify five fixed water molecules that play a significant role in substrate binding. Closure of the β6–α4 loop is revealed as essential not only for pyrophosphate recognition, but also for distal ribose orientation. In addition, a novel structural role for residue D40 is identified. Furthermore, it is revealed that OiMacroD not only catalyses the hydrolysis of O -acetyl-ADP-ribose but also reverses protein mono-ADP-ribosylation. Finally, mutant G37V supports the participation of a substrate-coordinated water molecule in catalysis that helps to select the proper substrate conformation.

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Alhammad, Yousef M. O., et Anthony R. Fehr. « The Viral Macrodomain Counters Host Antiviral ADP-Ribosylation ». Viruses 12, n^o 4 (31 mars 2020) : 384. http://dx.doi.org/10.3390/v12040384.

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Macrodomains, enzymes that remove ADP-ribose from proteins, are encoded by several families of RNA viruses and have recently been shown to counter innate immune responses to virus infection. ADP-ribose is covalently attached to target proteins by poly-ADP-ribose polymerases (PARPs), using nicotinamide adenine dinucleotide (NAD+) as a substrate. This modification can have a wide variety of effects on proteins including alteration of enzyme activity, protein–protein interactions, and protein stability. Several PARPs are induced by interferon (IFN) and are known to have antiviral properties, implicating ADP-ribosylation in the host defense response and suggesting that viral macrodomains may counter this response. Recent studies have demonstrated that viral macrodomains do counter the innate immune response by interfering with PARP-mediated antiviral defenses, stress granule formation, and pro-inflammatory cytokine production. Here, we will describe the known functions of the viral macrodomains and review recent literature demonstrating their roles in countering PARP-mediated antiviral responses.

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McPherson, Robert Lyle, Rachy Abraham, Easwaran Sreekumar, Shao-En Ong, Shang-Jung Cheng, Victoria K. Baxter, Hans A. V. Kistemaker, Dmitri V. Filippov, Diane E. Griffin et Anthony K. L. Leung. « ADP-ribosylhydrolase activity of Chikungunya virus macrodomain is critical for virus replication and virulence ». Proceedings of the National Academy of Sciences 114, n^o 7 (31 janvier 2017) : 1666–71. http://dx.doi.org/10.1073/pnas.1621485114.

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Chikungunya virus (CHIKV), an Old World alphavirus, is transmitted to humans by infected mosquitoes and causes acute rash and arthritis, occasionally complicated by neurologic disease and chronic arthritis. One determinant of alphavirus virulence is nonstructural protein 3 (nsP3) that contains a highly conserved MacroD-type macrodomain at the N terminus, but the roles of nsP3 and the macrodomain in virulence have not been defined. Macrodomain is a conserved protein fold found in several plus-strand RNA viruses that binds to the small molecule ADP-ribose. Prototype MacroD-type macrodomains also hydrolyze derivative linkages on the distal ribose ring. Here, we demonstrated that the CHIKV nsP3 macrodomain is able to hydrolyze ADP-ribose groups from mono(ADP-ribosyl)ated proteins. Using mass spectrometry, we unambiguously defined its substrate specificity as mono(ADP-ribosyl)ated aspartate and glutamate but not lysine residues. Mutant viruses lacking hydrolase activity were unable to replicate in mammalian BHK-21 cells or mosquitoAedes albopictuscells and rapidly reverted catalytically inactivating mutations. Mutants with reduced enzymatic activity had slower replication in mammalian neuronal cells and reduced virulence in 2-day-old mice. Therefore, nsP3 mono(ADP-ribosyl)hydrolase activity is critical for CHIKV replication in both vertebrate hosts and insect vectors, and for virulence in mice.

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Jia, Su-Jie, Si Jin, Fan Zhang, Fan Yi, William L. Dewey et Pin-Lan Li. « Formation and function of ceramide-enriched membrane platforms with CD38 during M1-receptor stimulation in bovine coronary arterial myocytes ». American Journal of Physiology-Heart and Circulatory Physiology 295, n^o 4 (octobre 2008) : H1743—H1752. http://dx.doi.org/10.1152/ajpheart.00617.2008.

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CD38 contains an ADP ribosylcyclase domain that mediates intracellular Ca2+ signaling by the production of cyclic ADP-ribose (cADPR), but the mechanisms by which the agonists activate this enzyme remain unclear. The present study tested a hypothesis that a special lipid-raft (LR) form, ceramide-enriched lipid platform, contributes to CD38 activation to produce cADPR in response to muscarinic type 1 (M1) receptor stimulation in bovine coronary arterial myocytes (CAMs). By confocal microscopic analysis, oxotremorine (Oxo), an M1 receptor agonist, was found to increase LR clustering on the membrane with the formation of a complex of CD38 and LR components such as GM1, acid sphingomyelinase (ASMase), and ceramide, a typical ceramide-enriched macrodomain. At 80 μM, Oxo increased LR clustering by 78.8%, which was abolished by LR disruptors, methyl-β-cyclodextrin (MCD), or filipin. With the use of a fluorescence resonance energy transfer (FRET) technique, 15.5 ± 1.9% energy transfer rate (vs. 5.3 ± 0.9% of control) between CD38 and LR component, ganglioside M1 was detected, further confirming the proximity of both molecules. In the presence of MCD or filipin, there were no FRET signals detected. In floated detergent-resistant membrane fractions, CD38 significantly increased in LR fractions of CAMs treated by Oxo. Moreover, MCD or filipin attenuated Oxo-induced production of cADPR via CD38. Functionally, Oxo-induced intracellular Ca2+ release and coronary artery constriction via cADPR were also blocked by LR disruption or ASMase inhibition. These results provide the first evidence that the formation of ceramide-enriched lipid macrodomains is crucial for Oxo-induced activation of CD38 to produce cADPR in CAMs, and these lipid macrodomains mediate transmembrane signaling of M1 receptor activation to produce second messenger cADPR.

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Gamble, Matthew J. « Expanding the functional repertoire of macrodomains ». Nature Structural & ; Molecular Biology 20, n^o 4 (avril 2013) : 407–8. http://dx.doi.org/10.1038/nsmb.2552.

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Xu, Guisheng, Haosu Luo, Zhenyi Qi, Haiqing Xu et Zhiwen Yin. « Domain configurations in relaxor ferroelectric single crystals Pb(Mg1/3Nb2/3)O3–PbTiO3 ». Journal of Materials Research 16, n^o 4 (avril 2001) : 932–37. http://dx.doi.org/10.1557/jmr.2001.0132.

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The 90° macrodomains in tetragonal Pb(Mg1/3Nb2/3)O3–PbTiO3 (PMNT) crystals take the shape of coarse and straight strips under optical microscopes and scanning electron acoustic microscopes. However, 71° or 109° domains in rhombohedral PMNT crystals are relatively poor in contrast and become clearer, coarser and straighter as their composition becomes closer to morphotropic phase boundaries, showing an evolution series of micro-to-macro domain transformation. Moreover, domain configurations are also dependent on the nucleation and growth rate of domains, the crystal defects, and the cooling rate through Curie temperature. The appearance of macrodomains arises from the strengthening of depolarization field and the weakening of random field.

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Zhang, Sixue, Atefeh Garzan, Nicole Haese, Robert Bostwick, Yohanka Martinez-Gzegozewska, Lynn Rasmussen, Daniel N. Streblow et al. « Pyrimidone inhibitors targeting Chikungunya Virus nsP3 macrodomain by fragment-based drug design ». PLOS ONE 16, n^o 1 (22 janvier 2021) : e0245013. http://dx.doi.org/10.1371/journal.pone.0245013.

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The macrodomain of nsP3 (nsP3MD) is highly conserved among the alphaviruses and ADP-ribosylhydrolase activity of Chikungunya Virus (CHIKV) nsP3MD is critical for CHIKV viral replication and virulence. No small molecule drugs targeting CHIKV nsP3 have been identified to date. Here we report small fragments that bind to nsP3MD which were discovered by virtually screening a fragment library and X-ray crystallography. These identified fragments share a similar scaffold, 2-pyrimidone-4-carboxylic acid, and are specifically bound to the ADP-ribose binding site of nsP3MD. Among the fragments, 2-oxo-5,6-benzopyrimidine-4-carboxylic acid showed anti-CHIKV activity with an IC50 of 23 μM. Our fragment-based drug discovery approach provides valuable information to further develop a specific and potent nsP3 inhibitor of CHIKV viral replication based on the 2-pyrimidone-4-carboxylic acid scaffold. In silico studies suggest this pyrimidone scaffold could also bind to the macrodomains of other alphaviruses and coronaviruses and thus, have potential pan-antiviral activity.

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Rack, Johannes Gregor Matthias, Dragutin Perina et Ivan Ahel. « Macrodomains : Structure, Function, Evolution, and Catalytic Activities ». Annual Review of Biochemistry 85, n^o 1 (2 juin 2016) : 431–54. http://dx.doi.org/10.1146/annurev-biochem-060815-014935.

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Wazir, Sarah, Mirko M. Maksimainen, Heli I. Alanen, Albert Galera-Prat et Lari Lehtiö. « Activity-Based Screening Assay for Mono-ADP-Ribosylhydrolases ». SLAS DISCOVERY : Advancing the Science of Drug Discovery 26, n^o 1 (12 juin 2020) : 67–76. http://dx.doi.org/10.1177/2472555220928911.

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ADP-ribosylation is a post-translational modification involved in the regulation of many vital cellular processes. This posttranslational modification is carried out by ADP-ribosyltransferases converting β-NAD+ into nicotinamide and a protein-linked ADP-ribosyl group or a chain of PAR. The reverse reaction, release of ADP-ribose from the acceptor molecule, is catalyzed by ADP-ribosylhydrolases. Several hydrolases contain a macrodomain fold, and activities of human macrodomain protein modules vary from reading or erasing mono- and poly-ADP-ribosylation. Macrodomains have been linked to diseases such as cancer, making them potential drug targets. Discovery of inhibitors requires robust biochemical tools mostly lacking for hydrolases, and here we describe an inhibitor screening assay against mono-ADP-ribosylhydrolyzing enzymes. The activity-based assay uses an α-NAD+, anomer of β-NAD+, which is accepted as a substrate by MacroD1, MacroD2, and ARH3 due to its resemblance to the protein-linked ADP-ribose. The amount of α-NAD+ present after hydrolysis is measured by chemically converting it on a microtiter plate to a fluorescent compound. We optimized the assay for MacroD2 and performed a proof-of-concept compound screening. Three compounds were identified as screening hits with micromolar potency. However, further characterization of the compounds identified them as protein destabilizers, excluding further follow-up studies. Validation and screening demonstrated the usability of the in vitro assay for MacroD2, and we also demonstrate the applicability of the assay as a tool for other human ADP-ribosylhydrolases.

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Lee, Hyunmi, Jimmy A. Rotolo, Judith Mesicek, Tuula Penate-Medina, Andreas Rimner, Wen-Chieh Liao, Xianglei Yin et al. « Mitochondrial Ceramide-Rich Macrodomains Functionalize Bax upon Irradiation ». PLoS ONE 6, n^o 6 (13 juin 2011) : e19783. http://dx.doi.org/10.1371/journal.pone.0019783.

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Hoch, Nicolas C. « Host ADP-ribosylation and the SARS-CoV-2 macrodomain ». Biochemical Society Transactions 49, n^o 4 (5 août 2021) : 1711–21. http://dx.doi.org/10.1042/bst20201212.

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The COVID-19 pandemic has prompted intense research efforts into elucidating mechanisms of coronavirus pathogenesis and to propose antiviral interventions. The interferon (IFN) response is the main antiviral component of human innate immunity and is actively suppressed by several non-structural SARS-CoV-2 proteins, allowing viral replication within human cells. Differences in IFN signalling efficiency and timing have emerged as central determinants of the variability of COVID-19 disease severity between patients, highlighting the need for an improved understanding of host–pathogen interactions that affect the IFN response. ADP-ribosylation is an underexplored post-translational modification catalyzed by ADP-ribosyl transferases collectively termed poly(ADP-ribose) polymerases (PARPs). Several human PARPs are induced by the IFN response and participate in antiviral defences by regulating IFN signalling itself, modulating host processes such as translation and protein trafficking, as well as directly modifying and inhibiting viral target proteins. SARS-CoV-2 and other viruses encode a macrodomain that hydrolyzes ADP-ribose modifications, thus counteracting antiviral PARP activity. This mini-review provides a brief overview of the known targets of IFN-induced ADP-ribosylation and the functions of viral macrodomains, highlighting several open questions in the field.

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Pardo, Lorena, Alvaro García, Klaus Brebøl, Elisa Mercadelli et Carmen Galassi. « Characterization of Nanostructured Phases and Peculiar Phase Transitions in BNBT Lead-Free Piezoceramics ». Advances in Science and Technology 90 (octobre 2014) : 12–18. http://dx.doi.org/10.4028/www.scientific.net/ast.90.12.

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Submicron-structured (Bi0.5Na0.5)0.94Ba0.06TiO3 (BNBT6) dense ceramics, from nanometric powder synthesized by sol gel auto-combustion at 500°C and obtained by hot-pressing (800°C-2h) and subsequent recrystallization at moderate temperature (1000-1050°C-1h), have been studied. In-situ measurements at the shear mode of electromechanical resonance of non-standard thickness-poled shear plates as a function of the temperature show higher depolarization temperature than measurements at the radial mode of thin disks. Shear mode related material coefficients are measurable up to 160°C, being k15≈30% and d15≈250 pC.N-1 at 130°C. Depolarization is a complex phenomena caused by a ferroelectric (FE) macrodomains thermal randomization and a phase transition from the field-induced FE phase to a relaxor phase. The early stage of such a transition involves a non-negligible piezoelectricity arising most probably by the percolative coexistence of ferroelectric macrodomains in the resonator under the given stress field for each resonance mode.

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Garab, G., et L. Mustárdy. « Role of LHCII-containing macrodomains in the structure, function and dynamics of grana ». Functional Plant Biology 26, n^o 7 (1999) : 649. http://dx.doi.org/10.1071/pp99069.

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In higher plants and green algae two types of thylakoids are distinguished, granum (stacked) and stroma (unstacked) thylakoids. They form a three-dimensional (3D) network with large lateral heterogeneity: photosystem II (PSII) and the associated main chlorophyll a/b light-harvesting complex (LHCII) are found predominantly in the stacked region, while PSI and LHCI are located mainly in the unstacked region of the membrane. This picture emerged from the discovery of the physical separation of the two photosystems (Boardman and Anderson 1964). Granal chloroplasts possess significant flexibility, which is essential for optimizing the photosynthetic machinery under various environmental conditions. However, our understanding concerning the assembly, structural dynamics and regulatory functions of grana is far from being complete. In this paper we overview the significance of the three-dimensional structure of grana in the absorption properties, ionic equilibrations, and in the diffusion of membrane components between the stacked and unstacked regions. Further, we discuss the role of chiral macrodomains in the grana. Lateral heterogeneity of thylakoid membranes is proposed to be a consequence of the formation of macrodomains constituted of LHCII and PSII; their long range order permits long distance migration of excitation energy, which explains the energetic connectivity of PSII particles. The ability of macrodomains to undergo light-induced reversible structural changes lends structural flexibility to the granum. In purified LHCII, which has also been shown to form stacked lamellar aggregates with long range chiral order, excitation energy migrates for large distances; these macroaggregates are also capable of undergoing light-induced reversible structural changes and fluorescence quenching. Hence, some basic properties of grana appear to originate from its main constituent, the LHCII.

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Garab, G., et L. Mustárdy. « Role of LHCII-containing macrodomains in the structure, function and dynamics of grana ». Functional Plant Biology 27, n^o 7 (2000) : 723. http://dx.doi.org/10.1071/pp99069_c1.

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In higher plants and green algae two types of thylakoids are distinguished, granum (stacked) and stroma (unstacked) thylakoids. They form a three-dimensional (3D) network with large lateral heterogeneity: photosystem II (PSII) and the associated main chlorophyll a/b light-harvesting complex (LHCII) are found predominantly in the stacked region, while PSI and LHCI are located mainly in the unstacked region of the membrane. This picture emerged from the discovery of the physical separation of the two photosystems (Boardman and Anderson 1964). Granal chloroplasts possess significant flexibility, which is essential for optimizing the photosynthetic machinery under various environmental conditions. However, our understanding concerning the assembly, structural dynamics and regulatory functions of grana is far from being complete. In this paper we overview the significance of the three-dimensional structure of grana in the absorption properties, ionic equilibrations, and in the diffusion of membrane components between the stacked and unstacked regions. Further, we discuss the role of chiral macrodomains in the grana. Lateral heterogeneity of thylakoid membranes is proposed to be a consequence of the formation of macrodomains constituted of LHCII and PSII; their long range order permits long distance migration of excitation energy, which explains the energetic connectivity of PSII particles. The ability of macrodomains to undergo light-induced reversible structural changes lends structural flexibility to the granum. In purified LHCII, which has also been shown to form stacked lamellar aggregates with long range chiral order, excitation energy migrates for large distances; these macroaggregates are also capable of undergoing light-induced reversible structural changes and fluorescence quenching. Hence, some basic properties of grana appear to originate from its main constituent, the LHCII.

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Garab, G., et L. Mustárdy. « Role of LHCII-containing macrodomains in the structure, function and dynamics of grana ». Functional Plant Biology 27, n^o 3 (2000) : 279. http://dx.doi.org/10.1071/pp99069_co.

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In higher plants and green algae two types of thylakoids are distinguished, granum (stacked) and stroma (unstacked) thylakoids. They form a three-dimensional (3D) network with large lateral heterogeneity: photosystem II (PSII) and the associated main chlorophyll a/b light-harvesting complex (LHCII) are found predominantly in the stacked region, while PSI and LHCI are located mainly in the unstacked region of the membrane. This picture emerged from the discovery of the physical separation of the two photosystems (Boardman and Anderson 1964). Granal chloroplasts possess significant flexibility, which is essential for optimizing the photosynthetic machinery under various environmental conditions. However, our understanding concerning the assembly, structural dynamics and regulatory functions of grana is far from being complete. In this paper we overview the significance of the three-dimensional structure of grana in the absorption properties, ionic equilibrations, and in the diffusion of membrane components between the stacked and unstacked regions. Further, we discuss the role of chiral macrodomains in the grana. Lateral heterogeneity of thylakoid membranes is proposed to be a consequence of the formation of macrodomains constituted of LHCII and PSII; their long range order permits long distance migration of excitation energy, which explains the energetic connectivity of PSII particles. The ability of macrodomains to undergo light-induced reversible structural changes lends structural flexibility to the granum. In purified LHCII, which has also been shown to form stacked lamellar aggregates with long range chiral order, excitation energy migrates for large distances; these macroaggregates are also capable of undergoing light-induced reversible structural changes and fluorescence quenching. Hence, some basic properties of grana appear to originate from its main constituent, the LHCII.

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Lee, Hyunmi, Jimmy A. Rotolo, Judith Mesicek, Tuula Penate-Medina, Andreas Rimner, Wen-Chieh Liao, Xianglei Yin et al. « Correction : Mitochondrial Ceramide-Rich Macrodomains Functionalize Bax upon Irradiation ». PLOS ONE 10, n^o 12 (30 décembre 2015) : e0146210. http://dx.doi.org/10.1371/journal.pone.0146210.

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Fehr, Anthony R., Gytis Jankevicius, Ivan Ahel et Stanley Perlman. « Viral Macrodomains : Unique Mediators of Viral Replication and Pathogenesis ». Trends in Microbiology 26, n^o 7 (juillet 2018) : 598–610. http://dx.doi.org/10.1016/j.tim.2017.11.011.

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Lapaque, Nicolas, Frederique Forquet, Chantal de Chastellier, Zohair Mishal, Gilles Jolly, Edgardo Moreno, Ignacio Moriyon, John E. Heuser, Hai-Tao He et Jean-Pierre Gorvel. « Characterization of Brucella abortus lipopolysaccharide macrodomains as mega rafts ». Cellular Microbiology 8, n^o 2 (février 2006) : 197–206. http://dx.doi.org/10.1111/j.1462-5822.2005.00609.x.

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Jiang, A. Q., Z. H. Chen, W. H. Song et L. D. Zhang. « Imaging the collapse of macrodomains from coupling defect-dipole relaxation ». Physical Review B 61, n^o 9 (1 mars 2000) : 5835–38. http://dx.doi.org/10.1103/physrevb.61.5835.

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Forst, Alexandra H., Tobias Karlberg, Nicolas Herzog, Ann-Gerd Thorsell, Annika Gross, Karla L. H. Feijs, Patricia Verheugd et al. « Recognition of Mono-ADP-Ribosylated ARTD10 Substrates by ARTD8 Macrodomains ». Structure 21, n^o 3 (mars 2013) : 462–75. http://dx.doi.org/10.1016/j.str.2012.12.019.

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Huang, Yuwei, Ben Zucker, Shaojin Zhang, Sharon Elias, Yun Zhu, Hui Chen, Tianlun Ding et al. « Migrasome formation is mediated by assembly of micron-scale tetraspanin macrodomains ». Nature Cell Biology 21, n^o 8 (août 2019) : 991–1002. http://dx.doi.org/10.1038/s41556-019-0367-5.

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Solymosi, K., K. Lenti, B. Myśliwa‐Kurdziel, J. Fidy, K. Strzałka et B. Böddi. « Hg2+Reacts with Different Components of the NADPH : Protochlorophyllide Oxidoreductase Macrodomains ». Plant Biology 6, n^o 3 (mai 2004) : 358–68. http://dx.doi.org/10.1055/s-2004-817893.

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Zuev, L. B. « Kinetics of Localized Plasticity Macrodomains at the Prefracture Stage in Metals ». Technical Physics 50, n^o 12 (2005) : 1636. http://dx.doi.org/10.1134/1.2148568.

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Lesterlin, Christian, Romain Mercier, Frédéric Boccard, François‐Xavier Barre et François Cornet. « Roles for replichores and macrodomains in segregation of the Escherichia coli chromosome ». EMBO reports 6, n^o 6 (juin 2005) : 557–62. http://dx.doi.org/10.1038/sj.embor.7400428.

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Ivry, Yachin, Vera Lyahovitskaya, Ilya Zon, Igor Lubomirsky, Ellen Wachtel et Alexander L. Roytburd. « Enhanced pyroelectric effect in self-supported films of BaTiO3 with polycrystalline macrodomains ». Applied Physics Letters 90, n^o 17 (23 avril 2007) : 172905. http://dx.doi.org/10.1063/1.2730749.

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Akbas, Mehmet A., Ian M. Reaney et William E. Lee. « Domain structure-property relations in lead lanthanum zirconate titanate ceramics ». Journal of Materials Research 11, n^o 9 (septembre 1996) : 2293–301. http://dx.doi.org/10.1557/jmr.1996.0292.

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The domain structure and dielectric properties as a function of lanthanum concentration and Zr/Ti ratio have been investigated in rhombohedral and tetragonal lead lanthanum zirconate titanate (PLZT) ceramics. Transmission electron microscopy revealed that, with increasing lanthanum concentration and Zr/Ti ratio, the long-range-ordered domains (macrodomains) reduced in width, initially being fine scale (20 nm) striations, but eventually forming a “mottled” contrast (5 nm), characteristic of a relaxor. Relative permittivity measurements as a function of temperature revealed a correlation between broadening of the dielectric maxima and the onset of relaxor-type behavior with the appearance of the striations and mottled (relaxor) contrast, respectively.

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Fijal, J., M. Zyla et M. Tokarz. « Chemical, sorptive and morphological properties of montmorillonite treated with ammonium bifluoride (NH4HF2) solutions ». Clay Minerals 20, n^o 1 (mars 1985) : 81–92. http://dx.doi.org/10.1180/claymin.1985.020.1.07.

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AbstractThe fluorination of montmorillonite by aqueous ammonium bifluoride solution (NH4HF2) has been investigated by chemical, sorptive, porosimetric and electron microscopic methods. Changes in the chemical composition of the montmorillonite during the fluorination were compared both in the crystal surface and in the bulk sample. The accumulation of fluorine was distinctly zonal, being present mainly in the surface layers. The electron microscope studies showed that the 300–400 nm thick macrodomains in the initial montmorillonite were cracked into small microdomains 20–30 nm in thickness, this resulting from disruption in the continuity of the octahedral sheets. These distinct changes in morphology of the montmorillonite aggregates particularly influenced the porosity and sorptive properties.

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Espéli, Olivier, et Frédéric Boccard. « Organization of the Escherichia coli chromosome into macrodomains and its possible functional implications ». Journal of Structural Biology 156, n^o 2 (novembre 2006) : 304–10. http://dx.doi.org/10.1016/j.jsb.2006.07.010.

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Huang, Yuwei, Ben Zucker, Shaojin Zhang, Sharon Elias, Yun Zhu, Hui Chen, Tianlun Ding et al. « Publisher Correction : Migrasome formation is mediated by assembly of micron-scale tetraspanin macrodomains ». Nature Cell Biology 21, n^o 10 (21 août 2019) : 1301. http://dx.doi.org/10.1038/s41556-019-0389-z.

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Ghitescu, Lucian, Bruce S. Jacobson et Philippe Crine. « A Novel, 85 KDA Endothelial Antigen Differentiates Plasma Membrane Macrodomains in Lung Alveolar Capillaries ». Endothelium 6, n^o 3 (janvier 1999) : 241–50. http://dx.doi.org/10.3109/10623329909053414.

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Tan, Jinzhi, Clemens Vonrhein, Oliver S. Smart, Gerard Bricogne, Michela Bollati, Yuri Kusov, Guido Hansen, Jeroen R. Mesters, Christian L. Schmidt et Rolf Hilgenfeld. « The SARS-unique domain of SARS-CoV contains two macrodomains that bind G-quadruplexes ». Acta Crystallographica Section A Foundations of Crystallography 65, a1 (16 août 2009) : s143. http://dx.doi.org/10.1107/s0108767309097128.

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Enoki, Thais A., Haden L. Scott, Gerald W. Feigenson et Frederick A. Heberle. « Inter- and Intra-Plane Interactions Control the Existence of Macrodomains in Asymmetric Giant Unilamellar Vesicles ». Biophysical Journal 120, n^o 3 (février 2021) : 147a. http://dx.doi.org/10.1016/j.bpj.2020.11.1080.

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Dame, Remus T., Olga J. Kalmykowa et David C. Grainger. « Chromosomal Macrodomains and Associated Proteins : Implications for DNA Organization and Replication in Gram Negative Bacteria ». PLoS Genetics 7, n^o 6 (16 juin 2011) : e1002123. http://dx.doi.org/10.1371/journal.pgen.1002123.

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Tan, Jinzhi, Clemens Vonrhein, Oliver S. Smart, Gerard Bricogne, Michela Bollati, Yuri Kusov, Guido Hansen, Jeroen R. Mesters, Christian L. Schmidt et Rolf Hilgenfeld. « The SARS-Unique Domain (SUD) of SARS Coronavirus Contains Two Macrodomains That Bind G-Quadruplexes ». PLoS Pathogens 5, n^o 5 (15 mai 2009) : e1000428. http://dx.doi.org/10.1371/journal.ppat.1000428.

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Pileni, M. P. « Control of the Size and Shape of Inorganic Nanocrystals at Various Scales from Nano to Macrodomains ». Journal of Physical Chemistry C 111, n^o 26 (juillet 2007) : 9019–38. http://dx.doi.org/10.1021/jp070646e.

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Boekema, Egbert J., Jan F. L. van Breemen, Henny van Roon et Jan P. Dekker. « Arrangement of photosystem II supercomplexes in crystalline macrodomains within the thylakoid membrane of green plant chloroplasts ». Journal of Molecular Biology 301, n^o 5 (septembre 2000) : 1123–33. http://dx.doi.org/10.1006/jmbi.2000.4037.

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Spiliotis, Elias T., et Michael A. McMurray. « Masters of asymmetry – lessons and perspectives from 50 years of septins ». Molecular Biology of the Cell 31, n^o 21 (1 octobre 2020) : 2289–97. http://dx.doi.org/10.1091/mbc.e19-11-0648.

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Septins are a unique family of GTPases, which were discovered 50 years ago as essential genes for the asymmetric cell shape and division of budding yeast. Septins assemble into filamentous nonpolar polymers, which associate with distinct membrane macrodomains and subpopulations of actin filaments and microtubules. While structurally a cytoskeleton-like element, septins function predominantly as spatial regulators of protein localization and interactions. Septin scaffolds and barriers have provided a long-standing paradigm for the generation and maintenance of asymmetry in cell membranes. Septins also promote asymmetry by regulating the spatial organization of the actin and microtubule cytoskeleton, and biasing the directionality of membrane traffic. In this 50th anniversary perspective, we highlight how septins have conserved and adapted their roles as effectors of membrane and cytoplasmic asymmetry across fungi and animals. We conclude by outlining principles of septin function as a module of symmetry breaking, which alongside the monomeric small GTPases provides a core mechanism for the biogenesis of molecular asymmetry and cell polarity.

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Zhang, Yulin, Jianyong Wang, Shijia Xing, Liuju Li, Shiqun Zhao, Wenzhen Zhu, Kuo Liang, Yanmei Liu et Liangyi Chen. « Mitochondria determine the sequential propagation of the calcium macrodomains revealed by the super-resolution calcium lantern imaging ». Science China Life Sciences 63, n^o 10 (8 avril 2020) : 1543–51. http://dx.doi.org/10.1007/s11427-019-1659-4.

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Solymosi, Katalin, László Smeller, Margareta Ryberg, Christer Sundqvist, Judit Fidy et Béla Böddi. « Molecular rearrangement in POR macrodomains as a reason for the blue shift of chlorophyllide fluorescence observed after phototransformation ». Biochimica et Biophysica Acta (BBA) - Biomembranes 1768, n^o 6 (juin 2007) : 1650–58. http://dx.doi.org/10.1016/j.bbamem.2007.02.022.

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Poltronieri, Palmiro. « Emerging Concepts on the Role of ADP-Ribosylation ». Challenges 11, n^o 1 (19 février 2020) : 3. http://dx.doi.org/10.3390/challe11010003.

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NAD+ has emerged as a crucial element in both bioenergetic and signaling pathways, since it acts as a key regulator of cellular and organism homeostasis. NAD+ is a coenzyme in redox reactions, a donor of adenosine diphosphate-ribose (ADPr) moieties in ADP-ribosylation reactions, and a substrate for sirtuins, a group of histone deacetylase enzymes that use NAD+ to remove acetyl groups from proteins. NAD+ is also a precursor of cyclic ADP-ribose, a second messenger in the release and signaling of Ca++, and of diadenosine tetraphosphate (Ap4A) and oligoadenylates (oligo2′-5′A)—two immune response-activating compounds. In the biological systems considered in this review, NAD+ is mostly consumed in ADP-ribose (ADPr) transfer reactions. In this review, the roles of these chemical products are discussed in biological systems, such as in animals, plants, fungi and bacteria. In the review, ADP-ribosylating enzymes are introduced, as well as the importance to restore the NAD+ pools in these systems. Finally, a special attention is presently focused on viral macrodomains, aimed to develop inhibitors to improve the immune response to viruses.

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Chang, Young-Sheng, Bo-Han Ko, Jyh-Cherng Ju, Hsin-Hou Chang, Su-Hua Huang et Cheng-Wen Lin. « SARS Unique Domain (SUD) of Severe Acute Respiratory Syndrome Coronavirus Induces NLRP3 Inflammasome-Dependent CXCL10-Mediated Pulmonary Inflammation ». International Journal of Molecular Sciences 21, n^o 9 (30 avril 2020) : 3179. http://dx.doi.org/10.3390/ijms21093179.

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Severe acute respiratory syndrome–associated coronavirus (SARS-CoV) initiates the cytokine/chemokine storm-mediated lung injury. The SARS-CoV unique domain (SUD) with three macrodomains (N, M, and C), showing the G-quadruplex binding activity, was examined the possible role in SARS pathogenesis in this study. The chemokine profile analysis indicated that SARS-CoV SUD significantly up-regulated the expression of CXCL10, CCL5 and interleukin (IL)-1β in human lung epithelial cells and in the lung tissues of the mice intratracheally instilled with the recombinant plasmids. Among the SUD subdomains, SUD-MC substantially activated AP-1-mediated CXCL10 expression in vitro. In the wild type mice, SARS-CoV SUD-MC triggered the pulmonary infiltration of macrophages and monocytes, inducing CXCL10-mediated inflammatory responses and severe diffuse alveolar damage symptoms. Moreover, SUD-MC actuated NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome-dependent pulmonary inflammation, as confirmed by the NLRP3 inflammasome inhibitor and the NLRP3−/− mouse model. This study demonstrated that SARS-CoV SUD modulated NLRP3 inflammasome-dependent CXCL10-mediated pulmonary inflammation, providing the potential therapeutic targets for developing the antiviral agents.

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Karlický, Václav, Zuzana Kmecová Materová, Irena Kurasová, Jakub Nezval, Michal Štroch, Győző Garab et Vladimír Špunda. « Accumulation of geranylgeranylated chlorophylls in the pigment-protein complexes of Arabidopsis thaliana acclimated to green light : effects on the organization of light-harvesting complex II and photosystem II functions ». Photosynthesis Research 149, n^o 1-2 (4 mai 2021) : 233–52. http://dx.doi.org/10.1007/s11120-021-00827-1.

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AbstractLight quality significantly influences plant metabolism, growth and development. Recently, we have demonstrated that leaves of barley and other plant species grown under monochromatic green light (500–590 nm) accumulated a large pool of chlorophyll a (Chl a) intermediates with incomplete hydrogenation of their phytyl chains. In this work, we studied accumulation of these geranylgeranylated Chls a and b in pigment-protein complexes (PPCs) of Arabidopsis plants acclimated to green light and their structural–functional consequences on the photosynthetic apparatus. We found that geranylgeranylated Chls are present in all major PPCs, although their presence was more pronounced in light-harvesting complex II (LHCII) and less prominent in supercomplexes of photosystem II (PSII). Accumulation of geranylgeranylated Chls hampered the formation of PSII and PSI super- and megacomplexes in the thylakoid membranes as well as their assembly into chiral macrodomains; it also lowered the temperature stability of the PPCs, especially that of LHCII trimers, which led to their monomerization and an anomaly in the photoprotective mechanism of non-photochemical quenching. Role of geranylgeranylated Chls in adverse effects on photosynthetic apparatus of plants acclimated to green light is discussed.

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Garcke, Harald, Johannes Kampmann, Andreas Rätz et Matthias Röger. « A coupled surface-Cahn–Hilliard bulk-diffusion system modeling lipid raft formation in cell membranes ». Mathematical Models and Methods in Applied Sciences 26, n^o 06 (12 avril 2016) : 1149–89. http://dx.doi.org/10.1142/s0218202516500275.

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We propose and investigate a model for lipid raft formation and dynamics in biological membranes. The model describes the lipid composition of the membrane and an interaction with cholesterol. To account for cholesterol exchange between cytosol and cell membrane we couple a bulk-diffusion to an evolution equation on the membrane. The latter describes the relaxation dynamics for an energy which takes lipid–phase separation and lipid–cholesterol interaction energy into account. It takes the form of an (extended) Cahn–Hilliard equation. Different laws for the exchange term represent equilibrium and nonequilibrium models. We present a thermodynamic justification, analyze the respective qualitative behavior and derive asymptotic reductions of the model. In particular we present a formal asymptotic expansion near the sharp interface limit, where the membrane is separated into two pure phases of saturated and unsaturated lipids, respectively. Finally we perform numerical simulations and investigate the long-time behavior of the model and its parameter dependence. Both the mathematical analysis and the numerical simulations show the emergence of raft-like structures in the nonequilibrium case whereas in the equilibrium case only macrodomains survive in the long-time evolution.

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