View source for 5jeo


==Phosphorylated Rotavirus NSP1 in complex with IRF-3==
<StructureSection load='5jeo' size='340' side='right'caption='[[5jeo]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5jeo]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Group_a_rotaviruses Group a rotaviruses] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JEO OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5JEO FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5jej|5jej]], [[5jel|5jel]], [[5jek|5jek]], [[5jem|5jem]], [[5jer|5jer]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IRF3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5jeo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jeo OCA], [http://pdbe.org/5jeo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jeo RCSB], [http://www.ebi.ac.uk/pdbsum/5jeo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jeo ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/IRF3_HUMAN IRF3_HUMAN]] Key transcriptional regulator of type I interferon (IFN)-dependent immune responses and plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Acts as a more potent activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA) gene and plays a critical role in both the early and late phases of the IFNA/B gene induction. Found in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, becomes phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization and association with CREB binding protein (CREBBP) to form dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I IFN and ISG genes. Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages. 
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== Publication Abstract from PubMed ==
Type I IFNs are key cytokines mediating innate antiviral immunity. cGMP-AMP synthase, ritinoic acid-inducible protein 1 (RIG-I)-like receptors, and Toll-like receptors recognize microbial double-stranded (ds)DNA, dsRNA, and LPS to induce the expression of type I IFNs. These signaling pathways converge at the recruitment and activation of the transcription factor IRF-3 (IFN regulatory factor 3). The adaptor proteins STING (stimulator of IFN genes), MAVS (mitochondrial antiviral signaling), and TRIF (TIR domain-containing adaptor inducing IFN-beta) mediate the recruitment of IRF-3 through a conserved pLxIS motif. Here we show that the pLxIS motif of phosphorylated STING, MAVS, and TRIF binds to IRF-3 in a similar manner, whereas residues upstream of the motif confer specificity. The structure of the IRF-3 phosphomimetic mutant S386/396E bound to the cAMP response element binding protein (CREB)-binding protein reveals that the pLxIS motif also mediates IRF-3 dimerization and activation. Moreover, rotavirus NSP1 (nonstructural protein 1) employs a pLxIS motif to target IRF-3 for degradation, but phosphorylation of NSP1 is not required for its activity. These results suggest a concerted mechanism for the recruitment and activation of IRF-3 that can be subverted by viral proteins to evade innate immune responses.

Structural basis for concerted recruitment and activation of IRF-3 by innate immune adaptor proteins.,Zhao B, Shu C, Gao X, Sankaran B, Du F, Shelton CL, Herr AB, Ji JY, Li P Proc Natl Acad Sci U S A. 2016 Jun 14;113(24):E3403-12. doi:, 10.1073/pnas.1603269113. Epub 2016 Jun 2. PMID:27302953<ref>PMID:27302953</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5jeo" style="background-color:#fffaf0;"></div>

==See Also==
*[[Interferon regulatory factor|Interferon regulatory factor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Group a rotaviruses]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Li, P]]
[[Category: Zhao, B]]
[[Category: Immune system]]
[[Category: Viral immuinity]]