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| | ==Lassa nucleoprotein with dsRNA reveals novel mechanism for immune suppression== | | ==Lassa nucleoprotein with dsRNA reveals novel mechanism for immune suppression== |
| - | <StructureSection load='4g9z' size='340' side='right' caption='[[4g9z]], [[Resolution|resolution]] 2.03Å' scene=''> | + | <StructureSection load='4g9z' size='340' side='right'caption='[[4g9z]], [[Resolution|resolution]] 2.03Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4g9z]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Lassj Lassj]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G9Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4G9Z FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4g9z]] is a 3 chain structure with sequence from [https://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=4G9Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G9Z FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3mwp|3mwp]], [[3mx5|3mx5]], [[3mx2|3mx2]], [[3mwt|3mwt]]</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=4g9z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g9z OCA], [https://pdbe.org/4g9z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g9z RCSB], [https://www.ebi.ac.uk/pdbsum/4g9z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g9z ProSAT]</span></td></tr> |
| - | <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 LASSJ])</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=4g9z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g9z OCA], [http://pdbe.org/4g9z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4g9z RCSB], [http://www.ebi.ac.uk/pdbsum/4g9z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4g9z ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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). | + | [https://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). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Nucleoprotein|Nucleoprotein]] | + | *[[Nucleoprotein 3D structures|Nucleoprotein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lassj]] | + | [[Category: Large Structures]] |
| - | [[Category: Dong, C]] | + | [[Category: Lassa virus Josiah]] |
| - | [[Category: Dong, H]] | + | [[Category: Dong C]] |
| - | [[Category: Huang, Q]] | + | [[Category: Dong H]] |
| - | [[Category: Jiang, X]] | + | [[Category: Huang Q]] |
| - | [[Category: Liang, Y]] | + | [[Category: Jiang X]] |
| - | [[Category: Ly, H]] | + | [[Category: Liang Y]] |
| - | [[Category: SSPF, Scottish Structural Proteomics Facility]]
| + | [[Category: Ly H]] |
| - | [[Category: Wang, W]] | + | [[Category: Wang W]] |
| - | [[Category: 3'-5'-ribonuclease]]
| + | |
| - | [[Category: Nuclease]]
| + | |
| - | [[Category: Scottish structural proteomics facility]]
| + | |
| - | [[Category: Sspf]]
| + | |
| - | [[Category: Structural genomic]]
| + | |
| - | [[Category: Viral protein-rna complex]]
| + | |
| Structural highlights
Function
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).
Publication Abstract from PubMed
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jiang X, Huang Q, Wang W, Dong H, Ly H, Liang Y, Dong C. Structures of arenaviral nucleoproteins with triphosphate dsRNA reveal a unique mechanism of immune suppression. J Biol Chem. 2013 Apr 24. PMID:23615902 doi:10.1074/jbc.M112.420521
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