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6ea9

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Structure of VACV Poxin in post-reactive state with Gp[2'-5']Ap[3']

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Retrieved from "http://52.214.119.220/wiki/index.php/6ea9"

Categories: Large Structures | Vaccinia virus WR | Eaglesham JB | Kranzusch PJ

@@ Line 3: / Line 3: @@
 <StructureSection load='6ea9' size='340' side='right'caption='[[6ea9]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6ea9]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Vaccw Vaccw]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EA9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EA9 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6ea9]] is a 5 chain structure with sequence from [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=6EA9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EA9 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9BG:2,5-GpAp'>9BG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VACWR184, B2R ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10254 VACCW])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9BG:2,5-GpAp'>9BG</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6ea9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ea9 OCA], [https://pdbe.org/6ea9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ea9 RCSB], [https://www.ebi.ac.uk/pdbsum/6ea9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ea9 ProSAT]</span></td></tr>
 </table>
-<div style="background-color:#fffaf0;">
+== Function ==
-== Publication Abstract from PubMed ==
+[https://www.uniprot.org/uniprot/POXIN_VACCW POXIN_VACCW] Nuclease that is responsible for viral evasion of host cGAS-STING innate immunity (PubMed:30728498). Cleaves 2',3'-cGAMP which is produced by host cGAS following recognition of cytosolic DNA and blocks the subsequent 2',3'-cGAMP-mediated activation of TMEM173/STING, which normally spreads to adjacent cells and activates the interferon and NF-kappa-B immune responses (PubMed:30728498).<ref>PMID:30728498</ref>
-Cytosolic DNA triggers innate immune responses through the activation of cyclic GMP-AMP synthase (cGAS) and production of the cyclic dinucleotide second messenger 2',3'-cyclic GMP-AMP (cGAMP)(1-4). 2',3'-cGAMP is a potent inducer of immune signalling; however, no intracellular nucleases are known to cleave 2',3'-cGAMP and prevent the activation of the receptor stimulator of interferon genes (STING)(5-7). Here we develop a biochemical screen to analyse 24 mammalian viruses, and identify poxvirus immune nucleases (poxins) as a family of 2',3'-cGAMP-degrading enzymes. Poxins cleave 2',3'-cGAMP to restrict STING-dependent signalling and deletion of the poxin gene (B2R) attenuates vaccinia virus replication in vivo. Crystal structures of vaccinia virus poxin in pre- and post-reactive states define the mechanism of selective 2',3'-cGAMP degradation through metal-independent cleavage of the 3'-5' bond, converting 2',3'-cGAMP into linear Gp[2'-5']Ap[3']. Poxins are conserved in mammalian poxviruses. In addition, we identify functional poxin homologues in the genomes of moths and butterflies and the baculoviruses that infect these insects. Baculovirus and insect host poxin homologues retain selective 2',3'-cGAMP degradation activity, suggesting an ancient role for poxins in cGAS-STING regulation. Our results define poxins as a family of 2',3'-cGAMP-specific nucleases and demonstrate a mechanism for how viruses evade innate immunity.
-Viral and metazoan poxins are cGAMP-specific nucleases that restrict cGAS-STING signalling.,Eaglesham JB, Pan Y, Kupper TS, Kranzusch PJ Nature. 2019 Feb;566(7743):259-263. doi: 10.1038/s41586-019-0928-6. Epub 2019 Feb, 6. PMID:30728498<ref>PMID:30728498</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 6ea9" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 22: / Line 15: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Vaccw]]
+[[Category: Vaccinia virus WR]]
-[[Category: Eaglesham, J B]]
+[[Category: Eaglesham JB]]
-[[Category: Kranzusch, P J]]
+[[Category: Kranzusch PJ]]
-[[Category: Cga]]
-[[Category: Cgamp]]
-[[Category: Hydrolase]]
-[[Category: Innate immunity]]
-[[Category: Nuclease]]
-[[Category: Poxvirus]]
-[[Category: Vaccina virus]]

6ea9

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Structure of VACV Poxin in post-reactive state with Gp[2'-5']Ap[3']

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