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| | <StructureSection load='6wt7' size='340' side='right'caption='[[6wt7]], [[Resolution|resolution]] 2.90Å' scene=''> | | <StructureSection load='6wt7' size='340' side='right'caption='[[6wt7]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6wt7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Cragi Cragi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WT7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6WT7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6wt7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Crassostrea_gigas Crassostrea gigas]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WT7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WT7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1SY:CGAMP'>1SY</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]] 2.9Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">XP_011430837.1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=29159 CRAGI])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1SY:CGAMP'>1SY</scene></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=6wt7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wt7 OCA], [http://pdbe.org/6wt7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6wt7 RCSB], [http://www.ebi.ac.uk/pdbsum/6wt7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6wt7 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=6wt7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wt7 OCA], [https://pdbe.org/6wt7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wt7 RCSB], [https://www.ebi.ac.uk/pdbsum/6wt7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wt7 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/STING_CRAGI STING_CRAGI] |
| - | Stimulator of interferon genes (STING) is a receptor in human cells that senses foreign cyclic dinucleotides released during bacterial infection and endogenous cyclic GMP-AMP signalling during viral infection and antitumour immunity(1-5). STING shares no structural homology with other known signalling proteins(6-9), limiting functional analysis and preventing explanation of the origin of cyclic dinucleotide signalling in mammalian innate immunity. Here we discover functional STING homologues encoded within prokaryotic defence islands and reveal a conserved mechanism of signal activation. Crystal structures of bacterial STING define a minimal homodimeric scaffold that selectively responds to c-di-GMP synthesized by a neighbouring cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzyme. Bacterial STING domains couple cyclic dinucleotide recognition with protein filament formation to drive TIR effector domain oligomerization and rapid NAD(+) cleavage. We reconstruct the evolutionary events following acquisition of STING into metazoan innate immunity and determine the structure of a full-length TIR-STING fusion from the Pacific oyster Crassostrea gigas. Comparative structural analysis demonstrates how metazoan-specific additions to the core STING scaffold enabled a switch from direct effector function to regulation of antiviral transcription. Together, our results explain the mechanism of STING-dependent signalling and reveal conservation of a functional cGAS-STING pathway in prokaryotic bacteriophage defence.
| + | |
| - | | + | |
| - | STING cyclic dinucleotide sensing originated in bacteria.,Morehouse BR, Govande AA, Millman A, Keszei AFA, Lowey B, Ofir G, Shao S, Sorek R, Kranzusch PJ Nature. 2020 Sep 2. pii: 10.1038/s41586-020-2719-5. doi:, 10.1038/s41586-020-2719-5. PMID:32877915<ref>PMID:32877915</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6wt7" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cragi]] | + | [[Category: Crassostrea gigas]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Govande, A A]] | + | [[Category: Govande AA]] |
| - | [[Category: Keszei, A F.A]] | + | [[Category: Keszei AFA]] |
| - | [[Category: Kranzusch, P J]] | + | [[Category: Kranzusch PJ]] |
| - | [[Category: Lowey, B]] | + | [[Category: Lowey B]] |
| - | [[Category: Millman, A]] | + | [[Category: Millman A]] |
| - | [[Category: Morehouse, B R]] | + | [[Category: Morehouse BR]] |
| - | [[Category: Ofir, G]] | + | [[Category: Ofir G]] |
| - | [[Category: Shao, S]] | + | [[Category: Shao S]] |
| - | [[Category: Sorek, R]] | + | [[Category: Sorek R]] |
| - | [[Category: Cyclic dinucleotide receptor]]
| + | |
| - | [[Category: Immune effector]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Tir domain]]
| + | |