8i9j

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'''Unreleased structure'''
 
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The entry 8i9j is ON HOLD until Paper Publication
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==The PKR and E3L complex==
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<StructureSection load='8i9j' size='340' side='right'caption='[[8i9j]], [[Resolution|resolution]] 6.39&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[8i9j]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Vaccinia_virus_WR Vaccinia virus WR]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8I9J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8I9J FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 6.39&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8i9j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8i9j OCA], [https://pdbe.org/8i9j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8i9j RCSB], [https://www.ebi.ac.uk/pdbsum/8i9j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8i9j ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PG065_VACCW PG065_VACCW] RNA-binding protein that plays a role in the inhibition of multiple cellular antiviral responses activated by double-stranded RNA (dsRNA), such as inhibition of PKR activation, necroptosis, and IFN-mediated antiviral activities (PubMed:1350676, PubMed:1681618, PubMed:18604270, PubMed:24257616, PubMed:25740987). Recognizes and binds Z-RNA structures via its Z-binding domain and dsRNA via its DRBM domain: RNA-binding activity is required to escape host ZBP1-dependent necroptosis (PubMed:29073079, PubMed:34192517). Mechanistically, the Z-binding domain binds Z-RNAs that are produced during vaccinia virus infection, thereby competing with Z-RNA detection by host ZBP1, suppressing ZBP1-dependent necroptosis (PubMed:34192517). Acts as a key inhibitor of the interferon response by blocking the phosphorylation and subsequent activation of IRF3 and IRF7 kinases that are required for interferon-alpha gene expression (PubMed:22419806). Inhibits NF-kappa-B activation and the ubiquitin-like protein ISG15, which is an early antiviral protein (PubMed:18604270, PubMed:24257616). The binding with host ISG15 subsequently blocks host ISGylation (PubMed:18604270, PubMed:24257616).<ref>PMID:1681618</ref> <ref>PMID:18604270</ref> <ref>PMID:22419806</ref> <ref>PMID:24257616</ref> <ref>PMID:25740987</ref> <ref>PMID:29073079</ref> <ref>PMID:34192517</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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E3L (RNA-binding protein E3) is one of the key IFN resistance genes encoded by VV and consists of 190 amino acids with a highly conserved carboxy-terminal double-stranded RNA-binding domain (dsRBD). PKR (dsRNA-dependent protein kinase) is an IFN-induced protein involved in anti-cell and antiviral activity. PKR inhibits the initiation of translation through alpha subunit of the initiation factor eIF2 (eIF2alpha) and mediates several transcription factors such as NF-kappaB, p53 or STATs. Activated PKR also induces apoptosis in vaccinia virus infection. E3L is required for viral IFN resistance and directly binds to PKR to block activation of PKR. In this work, we determined the three-dimensional complex structure of E3L and PKR using cryo-EM and determined the important residues involved in the interaction. In addition, PKR peptide binds to E3L and can increase protein levels of phosphorus-PKR and phosphorus-eIF2alpha-induced cell apoptosis through upregulation of phosphorus-PKR in HEK293 cells. Taken together, structural insights into E3L and PKR will provide a new optimization and development of vaccinia virus drugs.
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Authors: Han, C.W., Kim, H.J.
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Structural study of novel vaccinia virus E3L and dsRNA-dependent protein kinase complex.,Kim HJ, Han CW, Jeong MS, Jang SB Biochem Biophys Res Commun. 2023 Jul 12;665:1-9. doi: 10.1016/j.bbrc.2023.04.107. , Epub 2023 Apr 29. PMID:37146409<ref>PMID:37146409</ref>
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Description: The PKR and E3L complex
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Han, C.W]]
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<div class="pdbe-citations 8i9j" style="background-color:#fffaf0;"></div>
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[[Category: Kim, H.J]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Vaccinia virus WR]]
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[[Category: Han CW]]
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[[Category: Kim HJ]]

Current revision

The PKR and E3L complex

PDB ID 8i9j

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