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3kwi

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Revision as of 07:27, 5 August 2016

X-ray structure of NS1 effector domain W187Y mutant

Structural highlights

3kwi is a 2 chain structure with sequence from I72a2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	3ee9, 3ee8, 3kwg
Gene:	NS (I72A2)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[NS1_I72A2] 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.^[1] ^[2] ^[3] 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).^[4] ^[5] ^[6]

Publication Abstract from PubMed

The influenza A virus nonstructural protein NS1 is a multifunctional dimeric protein that acts as a potent inhibitor of the host cellular antiviral state. The C-terminal effector domain of NS1 binds host proteins, including CPSF30, and is a target for the development of new antiviral drugs. Here we present crystallographic structures of two mutant effector domains, W187Y and W187A, of influenza A/Udorn/72 virus. Unlike wild-type, the mutants behave exclusively as monomers in solution based on gel filtration data and light scattering. The W187Y mutant is able to bind CPSF30 with a binding affinity close to the wild-type protein; that is, it retains a receptor site for aromatic ligands nearly identical to the wild-type. Therefore, this monomeric mutant protein could serve as a drug target for a high throughput inhibitor screening assays, since its binding pocket is unoccupied in solution and potentially more accessible to small molecule ligands.

X-ray structures of NS1 effector domain mutants.,Xia S, Robertus JD Arch Biochem Biophys. 2010 Feb 15;494(2):198-204. Epub 2009 Dec 6. PMID:19995550^[7]

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

References

↑ Nemeroff ME, Barabino SM, Li Y, Keller W, Krug RM. Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs. Mol Cell. 1998 Jun;1(7):991-1000. PMID:9651582
↑ Li Y, Yamakita Y, Krug RM. Regulation of a nuclear export signal by an adjacent inhibitory sequence: the effector domain of the influenza virus NS1 protein. Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):4864-9. PMID:9560194
↑ Twu KY, Noah DL, Rao P, Kuo RL, Krug RM. The CPSF30 binding site on the NS1A protein of influenza A virus is a potential antiviral target. J Virol. 2006 Apr;80(8):3957-65. PMID:16571812 doi:10.1128/JVI.80.8.3957-3965.2006
↑ Nemeroff ME, Barabino SM, Li Y, Keller W, Krug RM. Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs. Mol Cell. 1998 Jun;1(7):991-1000. PMID:9651582
↑ Li Y, Yamakita Y, Krug RM. Regulation of a nuclear export signal by an adjacent inhibitory sequence: the effector domain of the influenza virus NS1 protein. Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):4864-9. PMID:9560194
↑ Twu KY, Noah DL, Rao P, Kuo RL, Krug RM. The CPSF30 binding site on the NS1A protein of influenza A virus is a potential antiviral target. J Virol. 2006 Apr;80(8):3957-65. PMID:16571812 doi:10.1128/JVI.80.8.3957-3965.2006
↑ Xia S, Robertus JD. X-ray structures of NS1 effector domain mutants. Arch Biochem Biophys. 2010 Feb 15;494(2):198-204. Epub 2009 Dec 6. PMID:19995550 doi:10.1016/j.abb.2009.12.008

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/3kwi"

@@ Line 1: / Line 1: @@
 ==X-ray structure of NS1 effector domain W187Y mutant==
 <StructureSection load='3kwi' size='340' side='right' caption='[[3kwi]], [[Resolution|resolution]] 2.21&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3kwi]] 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=3KWI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KWI FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3kwi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/I72a2 I72a2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KWI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KWI FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ee9|3ee9]], [[3ee8|3ee8]], [[3kwg|3kwg]]</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=381517 I72A2])</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=3kwi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kwi OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3kwi RCSB], [http://www.ebi.ac.uk/pdbsum/3kwi 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=3kwi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kwi OCA], [http://pdbe.org/3kwi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kwi RCSB], [http://www.ebi.ac.uk/pdbsum/3kwi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3kwi 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 3kwi" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Influenza a virus]]
+[[Category: I72a2]]
 [[Category: Robertus, J D]]
 [[Category: Xia, S]]

3kwi

From Proteopedia

Revision as of 07:27, 5 August 2016

X-ray structure of NS1 effector domain W187Y mutant

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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