4fvu
From Proteopedia
(Difference between revisions)
| Line 4: | Line 4: | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4fvu]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Lassa_virus_Josiah Lassa virus Josiah] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FVU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FVU FirstGlance]. <br> | <table><tr><td colspan='2'>[[4fvu]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Lassa_virus_Josiah Lassa virus Josiah] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FVU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FVU FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.91Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=4fvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fvu OCA], [https://pdbe.org/4fvu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fvu RCSB], [https://www.ebi.ac.uk/pdbsum/4fvu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fvu ProSAT]</span></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=4fvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fvu OCA], [https://pdbe.org/4fvu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fvu RCSB], [https://www.ebi.ac.uk/pdbsum/4fvu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fvu ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[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). | [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;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Lassa virus causes hemorrhagic fever characterized by immunosuppression. The nucleoprotein of Lassa virus, termed NP, binds the viral genome. It also has an additional enzymatic activity as an exonuclease that specifically digests double-stranded RNA (dsRNA). dsRNA is a strong signal to the innate immune system of viral infection. Digestion of dsRNA by the NP exonuclease activity appears to cause suppression of innate immune signaling in the infected cell. Although the fold of the NP enzyme is conserved and the active site completely conserved with other exonucleases in its DEDDh family, NP is atypical among exonucleases in its preference for dsRNA and its strict specificity for one substrate. Here, we present the crystal structure of Lassa virus NP in complex with dsRNA. We find that unlike the exonuclease in Klenow fragment, the double-stranded nucleic acid in complex with Lassa NP remains base-paired instead of splitting, and that binding of the paired complementary strand is achieved by "relocation" of a basic loop motif from its typical exonuclease position. Further, we find that just one single glycine that contacts the substrate strand and one single tyrosine that stacks with a base of the complementary, non-substrate strand are responsible for the unique substrate specificity. This work thus provides templates for development of antiviral drugs that would be specific for viral, rather than host exonucleases of similar fold and active site, and illustrates how a very few amino acid changes confer alternate specificity and biological phenotype to an enzyme. | ||
| - | |||
| - | Structural Basis for the dsRNA Specificity of the Lassa Virus NP Exonuclease.,Hastie KM, King LB, Zandonatti MA, Saphire EO PLoS One. 2012;7(8):e44211. Epub 2012 Aug 28. PMID:22937163<ref>PMID:22937163</ref> | ||
| - | |||
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4fvu" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Nucleoprotein 3D structures|Nucleoprotein 3D structures]] | *[[Nucleoprotein 3D structures|Nucleoprotein 3D structures]] | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Structural basis for the dsRNA specificity of the Lassa virus NP exonuclease
| |||||||||||
