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2zko

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{{STRUCTURE_2zko| PDB=2zko | SCENE= }}
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==Structural basis for dsRNA recognition by NS1 protein of human influenza virus A==
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===Structural basis for dsRNA recognition by NS1 protein of human influenza virus A===
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<StructureSection load='2zko' size='340' side='right' caption='[[2zko]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
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{{ABSTRACT_PUBMED_18813227}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2zko]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/9infa 9infa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZKO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZKO 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=GOL:GLYCEROL'>GOL</scene></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=2zko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zko OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2zko RCSB], [http://www.ebi.ac.uk/pdbsum/2zko 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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Influenza A viruses are important human pathogens causing periodic pandemic threats. Nonstructural protein 1 (NS1) protein of influenza A virus (NS1A) shields the virus against host defense. Here, we report the crystal structure of NS1A RNA-binding domain (RBD) bound to a double-stranded RNA (dsRNA) at 1.7A. NS1A RBD forms a homodimer to recognize the major groove of A-form dsRNA in a length-independent mode by its conserved concave surface formed by dimeric anti-parallel alpha-helices. dsRNA is anchored by a pair of invariable arginines (Arg38) from both monomers by extensive hydrogen bonds. In accordance with the structural observation, isothermal titration calorimetry assay shows that the unique Arg38-Arg38 pair and two Arg35-Arg46 pairs are crucial for dsRNA binding, and that Ser42 and Thr49 are also important for dsRNA binding. Agrobacterium co-infiltration assay further supports that the unique Arg38 pair plays important roles in dsRNA binding in vivo.Cell Research advance online publication 23 September 2008; doi: 10.1038/cr.2008.288.
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==Function==
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Structural basis for dsRNA recognition by NS1 protein of influenza A virus.,Cheng A, Wong SM, Yuan YA Cell Res. 2008 Sep 23. PMID:18813227<ref>PMID:18813227</ref>
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[[http://www.uniprot.org/uniprot/NS1_I34A1 NS1_I34A1]] Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage and polyadenylation specificity factor (CPSF4) and the poly(A)-binding protein 2 (PABPN1). This results in the accumulation of unprocessed 3' end pre-mRNAs which can't be exported from the nucleus. Cellular protein synthesis is thereby shut off very early after virus infection. Viral protein synthesis is not affected by the inhibition of the cellular 3' end processing machinery because the poly(A) tails of viral mRNAs are produced by the viral polymerase through a stuttering mechanism (By similarity). Prevents the establishment of the cellular antiviral state by inhibiting TRIM25-mediated DDX58 ubiquitination, which normally triggers the antiviral transduction signal that leads to the activation of type I IFN genes by transcription factors like IRF3 and IRF7. Prevents human EIF2AK2/PKR activation, either by binding double-strand RNA, or by interacting directly with EIF2AK2/PKR. This function may be important at the very beginning of the infection, when NS1 is mainly present in the cytoplasm. Also binds poly(A) and U6 snRNA. Suppresses the RNA silencing-based antiviral response in Drosophila cells (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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[[2zko]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/9infa 9infa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZKO OCA].
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</div>
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:018813227</ref><references group="xtra"/><references/>
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__TOC__
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[[Category: 9infa]]
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</StructureSection>
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[[Category: Yuan, Y A.]]
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[[Category: Yuan, Y A]]
[[Category: Dsrna]]
[[Category: Dsrna]]
[[Category: Host-virus interaction]]
[[Category: Host-virus interaction]]

Revision as of 18:40, 21 December 2014

Structural basis for dsRNA recognition by NS1 protein of human influenza virus A

2zko, resolution 1.70Å

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