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| ==High-resolution solid-state NMR structure of the helical signal transduction filament MAVS CARD== | | ==High-resolution solid-state NMR structure of the helical signal transduction filament MAVS CARD== |
| <StructureSection load='2ms7' size='340' side='right' caption='[[2ms7]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''> | | <StructureSection load='2ms7' size='340' side='right'caption='[[2ms7]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[2ms7]] is a 21 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MS7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MS7 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[2ms7]] is a 21 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MS7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MS7 FirstGlance]. <br> |
| </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ms7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ms7 OCA], [http://pdbe.org/2ms7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ms7 RCSB], [http://www.ebi.ac.uk/pdbsum/2ms7 PDBsum]</span></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solid-state NMR</td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ms7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ms7 OCA], [https://pdbe.org/2ms7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ms7 RCSB], [https://www.ebi.ac.uk/pdbsum/2ms7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ms7 ProSAT]</span></td></tr> |
| </table> | | </table> |
| {{Large structure}}
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| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/MAVS_HUMAN MAVS_HUMAN]] Required for innate immune defense against viruses. Acts downstream of DDX58/RIG-I and IFIH1/MDA5, which detect intracellular dsRNA produced during viral replication, to coordinate pathways leading to the activation of NF-kappa-B, IRF3 and IRF7, and to the subsequent induction of antiviral cytokines such as IFN-beta and RANTES (CCL5). Peroxisomal and mitochondrial MAVS act sequentially to create an antiviral cellular state. Upon viral infection, peroxisomal MAVS induces the rapid interferon-independent expression of defense factors that provide short-term protection, whereas mitochondrial MAVS activates an interferon-dependent signaling pathway with delayed kinetics, which amplifies and stabilizes the antiviral response. May activate the same pathways following detection of extracellular dsRNA by TLR3. May protect cells from apoptosis.<ref>PMID:16125763</ref> <ref>PMID:16153868</ref> <ref>PMID:16177806</ref> <ref>PMID:16127453</ref> <ref>PMID:19631370</ref> <ref>PMID:20451243</ref> | | [https://www.uniprot.org/uniprot/MAVS_HUMAN MAVS_HUMAN] Required for innate immune defense against viruses. Acts downstream of DDX58/RIG-I and IFIH1/MDA5, which detect intracellular dsRNA produced during viral replication, to coordinate pathways leading to the activation of NF-kappa-B, IRF3 and IRF7, and to the subsequent induction of antiviral cytokines such as IFN-beta and RANTES (CCL5). Peroxisomal and mitochondrial MAVS act sequentially to create an antiviral cellular state. Upon viral infection, peroxisomal MAVS induces the rapid interferon-independent expression of defense factors that provide short-term protection, whereas mitochondrial MAVS activates an interferon-dependent signaling pathway with delayed kinetics, which amplifies and stabilizes the antiviral response. May activate the same pathways following detection of extracellular dsRNA by TLR3. May protect cells from apoptosis.<ref>PMID:16125763</ref> <ref>PMID:16153868</ref> <ref>PMID:16177806</ref> <ref>PMID:16127453</ref> <ref>PMID:19631370</ref> <ref>PMID:20451243</ref> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| The controlled formation of filamentous protein complexes plays a crucial role in many biological systems and represents an emerging paradigm in signal transduction. The mitochondrial antiviral signaling protein (MAVS) is a central signal transduction hub in innate immunity that is activated by a receptor-induced conversion into helical superstructures (filaments) assembled from its globular caspase activation and recruitment domain. Solid-state NMR (ssNMR) spectroscopy has become one of the most powerful techniques for atomic resolution structures of protein fibrils. However, for helical filaments, the determination of the correct symmetry parameters has remained a significant hurdle for any structural technique and could thus far not be precisely derived from ssNMR data. Here, we solved the atomic resolution structure of helical MAVS(CARD) filaments exclusively from ssNMR data. We present a generally applicable approach that systematically explores the helical symmetry space by efficient modeling of the helical structure restrained by interprotomer ssNMR distance restraints. Together with classical automated NMR structure calculation, this allowed us to faithfully determine the symmetry that defines the entire assembly. To validate our structure, we probed the protomer arrangement by solvent paramagnetic resonance enhancement, analysis of chemical shift differences relative to the solution NMR structure of the monomer, and mutagenesis. We provide detailed information on the atomic contacts that determine filament stability and describe mechanistic details on the formation of signaling-competent MAVS filaments from inactive monomers.
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| Structure determination of helical filaments by solid-state NMR spectroscopy.,He L, Bardiaux B, Ahmed M, Spehr J, Konig R, Lunsdorf H, Rand U, Luhrs T, Ritter C Proc Natl Acad Sci U S A. 2016 Jan 19;113(3):E272-81. doi:, 10.1073/pnas.1513119113. Epub 2016 Jan 5. PMID:26733681<ref>PMID:26733681</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 2ms7" style="background-color:#fffaf0;"></div>
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| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Bardiaux, B]] | | [[Category: Homo sapiens]] |
| [[Category: He, L]] | | [[Category: Large Structures]] |
| [[Category: Luehrs, T]] | | [[Category: Bardiaux B]] |
| [[Category: Ritter, C]] | | [[Category: He L]] |
| [[Category: Spehr, J]] | | [[Category: Luehrs T]] |
| [[Category: Mavs card filament]] | | [[Category: Ritter C]] |
| [[Category: Protein binding]] | | [[Category: Spehr J]] |