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3oa9

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Revision as of 22:12, 4 August 2016

Effector domain of influenza A/Duck/Albany/76 NS1

Structural highlights

3oa9 is a 2 chain structure with sequence from I76a2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	3d6r, 3o9q, 3o9r, 3o9s, 3o9t, 3o9u
Gene:	NS (I76A2)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[NS1_I76A2] 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 virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal 'tail'. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed 'helix-closed' and 'helix-open') in virus-infected cells. 'Helix-closed' conformations appear to enhance dsRNA binding, and 'helix-open' conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins.

A Transient Homotypic Interaction Model for the Influenza A Virus NS1 Protein Effector Domain.,Kerry PS, Ayllon J, Taylor MA, Hass C, Lewis A, Garcia-Sastre A, Randall RE, Hale BG, Russell RJ PLoS One. 2011 Mar 28;6(3):e17946. PMID:21464929^[1]

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

References

↑ Kerry PS, Ayllon J, Taylor MA, Hass C, Lewis A, Garcia-Sastre A, Randall RE, Hale BG, Russell RJ. A Transient Homotypic Interaction Model for the Influenza A Virus NS1 Protein Effector Domain. PLoS One. 2011 Mar 28;6(3):e17946. PMID:21464929 doi:10.1371/journal.pone.0017946

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/3oa9"

@@ Line 1: / Line 1: @@
 ==Effector domain of influenza A/Duck/Albany/76 NS1==
 <StructureSection load='3oa9' size='340' side='right' caption='[[3oa9]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3oa9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus Influenza a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OA9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OA9 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3oa9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/I76a2 I76a2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OA9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OA9 FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3d6r|3d6r]], [[3o9q|3o9q]], [[3o9r|3o9r]], [[3o9s|3o9s]], [[3o9t|3o9t]], [[3o9u|3o9u]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11320 Influenza A virus])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=385582 I76A2])</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=3oa9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oa9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3oa9 RCSB], [http://www.ebi.ac.uk/pdbsum/3oa9 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=3oa9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oa9 OCA], [http://pdbe.org/3oa9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3oa9 RCSB], [http://www.ebi.ac.uk/pdbsum/3oa9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3oa9 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3oa9" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Influenza a virus]]
+[[Category: I76a2]]
 [[Category: Hale, B G]]
 [[Category: Hass, C]]

3oa9

From Proteopedia

Revision as of 22:12, 4 August 2016

Effector domain of influenza A/Duck/Albany/76 NS1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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