4gv3

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{{STRUCTURE_4gv3| PDB=4gv3 | SCENE= }}
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==Structures of Lassa and Tacaribe viral nucleoproteins with or without 5 triphosphate dsRNA substrate reveal a unique 3 -5 exoribonuclease mechanism to suppress type I interferon production==
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===Structures of Lassa and Tacaribe viral nucleoproteins with or without 5 triphosphate dsRNA substrate reveal a unique 3 -5 exoribonuclease mechanism to suppress type I interferon production===
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<StructureSection load='4gv3' size='340' side='right' caption='[[4gv3]], [[Resolution|resolution]] 1.68&Aring;' scene=''>
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{{ABSTRACT_PUBMED_23615902}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4gv3]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Lassa_virus_josiah Lassa virus josiah]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GV3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GV3 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3mwp|3mwp]], [[4g9z|4g9z]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">N ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11622 Lassa virus Josiah])</td></tr>
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<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=4gv3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gv3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gv3 RCSB], [http://www.ebi.ac.uk/pdbsum/4gv3 PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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A hallmark of severe Lassa fever is the generalized immune suppression, the mechanism of which is poorly understood. Lassa virus (LASV) nucleoprotein (NP) is the only known 3-5 exoribonuclease that can suppress type I interferon (IFN) production possibly by degrading immune-stimulatory RNAs. How this unique enzymatic activity of LASV NP recognizes and processes RNA substrates is unknown. We provide an atomic view of a catalytically active exoribonuclease domain of LASV NP (LASV NP-C) in the process of degrading a 5 triphosphate double-stranded (ds) RNA substrate - a typical pathogen-associated molecular pattern (PAMP) molecule - to induce type I IFN production. Additionally, we provide for the first time a high-resolution crystal structure of an active exoribonuclease domain of Tacaribe arenavirus (TCRV) NP. Coupled with the in vitro enzymatic and cell-based interferon suppression assays, these structural analyses strongly support a unified model of an exoribonuclease-dependent IFN suppression mechanism shared by all known arenaviruses. New knowledge learned from these studies should aid the development of therapeutics against pathogenic arenaviruses that can infect hundreds of thousand individuals and kill thousands annually.
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==Function==
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Structures of arenaviral nucleoproteins with triphosphate dsRNA reveal a unique mechanism of immune suppression.,Jiang X, Huang Q, Wang W, Dong H, Ly H, Liang Y, Dong C J Biol Chem. 2013 Apr 24. PMID:23615902<ref>PMID:23615902</ref>
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[[http://www.uniprot.org/uniprot/NCAP_LASSJ NCAP_LASSJ]] Encapsidates the genome, protecting it from nucleases. The encapsidated genomic RNA is termed the nucleocapsid (NC). Serves as template for viral transcription and replication. The increased presence of protein N in host cell does not seem to trigger the switch from transcription to replication as observed in other negative strain RNA viruses. Disables the host innate defense by interfering with beta interferon (IFN-beta) production. Strongly inhibits the nuclear translocation of IRF3, a protein involved in IFN activation pathway. Also inhibits the activation of IFN-beta and IRF3-dependent promoters (By similarity).
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[4gv3]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Lassa_virus_josiah Lassa virus josiah]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GV3 OCA].
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</div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:023615902</ref><references group="xtra"/><references/>
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*[[Nucleoprotein|Nucleoprotein]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Lassa virus josiah]]
[[Category: Lassa virus josiah]]
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[[Category: Dong, C.]]
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[[Category: Dong, C]]
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[[Category: Dong, H.]]
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[[Category: Dong, H]]
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[[Category: Huang, Q.]]
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[[Category: Huang, Q]]
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[[Category: Jiang, X.]]
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[[Category: Jiang, X]]
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[[Category: Liang, Y.]]
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[[Category: Liang, Y]]
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[[Category: Ly, H.]]
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[[Category: Ly, H]]
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[[Category: Wang, W.]]
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[[Category: Wang, W]]
[[Category: 3'-5'exoribonuclease]]
[[Category: 3'-5'exoribonuclease]]
[[Category: Ddedh family]]
[[Category: Ddedh family]]
[[Category: Rna binding protein-rna complex]]
[[Category: Rna binding protein-rna complex]]

Revision as of 10:44, 21 December 2014

Structures of Lassa and Tacaribe viral nucleoproteins with or without 5 triphosphate dsRNA substrate reveal a unique 3 -5 exoribonuclease mechanism to suppress type I interferon production

4gv3, resolution 1.68Å

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