|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6ea6' size='340' side='right'caption='[[6ea6]], [[Resolution|resolution]] 1.70Å' scene=''> | | <StructureSection load='6ea6' size='340' side='right'caption='[[6ea6]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ea6]] is a 4 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=6EA6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EA6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ea6]] is a 4 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=6EA6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EA6 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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]] 1.703Å</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=MSE:SELENOMETHIONINE'>MSE</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=6ea6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ea6 OCA], [https://pdbe.org/6ea6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ea6 RCSB], [https://www.ebi.ac.uk/pdbsum/6ea6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ea6 ProSAT]</span></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=6ea6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ea6 OCA], [https://pdbe.org/6ea6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ea6 RCSB], [https://www.ebi.ac.uk/pdbsum/6ea6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ea6 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 22: |
Line 24: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[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]]
| + | |
| Structural highlights
Function
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).[1]
Publication Abstract from PubMed
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Eaglesham JB, Pan Y, Kupper TS, Kranzusch PJ. Viral and metazoan poxins are cGAMP-specific nucleases that restrict cGAS-STING signalling. Nature. 2019 Feb;566(7743):259-263. doi: 10.1038/s41586-019-0928-6. Epub 2019 Feb, 6. PMID:30728498 doi:http://dx.doi.org/10.1038/s41586-019-0928-6
- ↑ Eaglesham JB, Pan Y, Kupper TS, Kranzusch PJ. Viral and metazoan poxins are cGAMP-specific nucleases that restrict cGAS-STING signalling. Nature. 2019 Feb;566(7743):259-263. doi: 10.1038/s41586-019-0928-6. Epub 2019 Feb, 6. PMID:30728498 doi:http://dx.doi.org/10.1038/s41586-019-0928-6
|
