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2zko

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Revision as of 12:38, 5 August 2016

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

Structural highlights

2zko is a 4 chain structure with sequence from 9infa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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).

Publication Abstract from PubMed

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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Cheng A, Wong SM, Yuan YA. Structural basis for dsRNA recognition by NS1 protein of influenza A virus. Cell Res. 2008 Sep 23. PMID:18813227 doi:http://dx.doi.org/cr2008288

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2zko"

@@ Line 1: / Line 1: @@
 ==Structural basis for dsRNA recognition by NS1 protein of human influenza virus A==
 <StructureSection load='2zko' size='340' side='right' caption='[[2zko]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <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>
 </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>
-<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>
+<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://pdbe.org/2zko PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zko RCSB], [http://www.ebi.ac.uk/pdbsum/2zko PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2zko ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2zko" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

2zko

From Proteopedia

Revision as of 12:38, 5 August 2016

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

Structural highlights

Function

Publication Abstract from PubMed

References

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Proteopedia Page Contributors and Editors (what is this?)

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