7uq2
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7uq2]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Tequatrovirus Tequatrovirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UQ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UQ2 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7uq2]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Tequatrovirus Tequatrovirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UQ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UQ2 FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4BW:2-AMINO-9-[(2R,3R,3AS,5R,7AR,9R,10R,10AS,12R,14AR)-9-(6-AMINO-9H-PURIN-9-YL)-3,5,10,12-TETRAHYDROXY-5,12-DIOXIDOOCTAHYDRO-2H,7H-DIFURO[3,2-D 3,2-J][1,3,7,9,2,8]TETRAOXADIPHOSPHACYCLODODECIN-2-YL]-1,9-DIHYDRO-6H-PURIN-6-ONE'>4BW</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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]] 2Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4BW:2-AMINO-9-[(2R,3R,3AS,5R,7AR,9R,10R,10AS,12R,14AR)-9-(6-AMINO-9H-PURIN-9-YL)-3,5,10,12-TETRAHYDROXY-5,12-DIOXIDOOCTAHYDRO-2H,7H-DIFURO[3,2-D 3,2-J][1,3,7,9,2,8]TETRAOXADIPHOSPHACYCLODODECIN-2-YL]-1,9-DIHYDRO-6H-PURIN-6-ONE'>4BW</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=7uq2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uq2 OCA], [https://pdbe.org/7uq2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uq2 RCSB], [https://www.ebi.ac.uk/pdbsum/7uq2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uq2 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=7uq2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uq2 OCA], [https://pdbe.org/7uq2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uq2 RCSB], [https://www.ebi.ac.uk/pdbsum/7uq2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uq2 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | [https://www.uniprot.org/uniprot/ | + | [https://www.uniprot.org/uniprot/ACB2_BPT4 ACB2_BPT4] Antagonizes CBASS (cyclic oligonucleotide-based antiphage signaling system) (Probable) (PubMed:36848932). Binds and sequesters host-produced 3',3'-cyclic GMP-AMP (cGAMP) with a dissociation constant of about 30 nM; each homohexamer binds 3 cGAMP molecules with 1 cGAMP molecule binding to 2 monomers (PubMed:36848932). Sequestration of cGAMP inhibits the cGAMP-activated phospholipase activity of host CBASS effector protein CapV (PubMed:36848932).<ref>PMID:36848932</ref> <ref>PMID:36848932</ref> |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | cGAS is an evolutionarily conserved enzyme that has a pivotal role in immune defence against infection(1-3). In vertebrate animals, cGAS is activated by DNA to produce cyclic GMP-AMP (cGAMP)(4,5), which leads to the expression of antimicrobial genes(6,7). In bacteria, cyclic dinucleotide (CDN)-based anti-phage signalling systems (CBASS) have been discovered(8-11). These systems are composed of cGAS-like enzymes and various effector proteins that kill bacteria on phage infection, thereby stopping phage spread. Of the CBASS systems reported, approximately 39% contain Cap2 and Cap3, which encode proteins with homology to ubiquitin conjugating (E1/E2) and deconjugating enzymes, respectively(8,12). Although these proteins are required to prevent infection of some bacteriophages(8), the mechanism by which the enzymatic activities exert an anti-phage effect is unknown. Here we show that Cap2 forms a thioester bond with the C-terminal glycine of cGAS and promotes conjugation of cGAS to target proteins in a process that resembles ubiquitin conjugation. The covalent conjugation of cGAS increases the production of cGAMP. Using a genetic screen, we found that the phage protein Vs.4 antagonized cGAS signalling by binding tightly to cGAMP (dissociation constant of approximately 30 nM) and sequestering it. A crystal structure of Vs.4 bound to cGAMP showed that Vs.4 formed a hexamer that was bound to three molecules of cGAMP. These results reveal a ubiquitin-like conjugation mechanism that regulates cGAS activity in bacteria and illustrates an arms race between bacteria and viruses through controlling CDN levels. | ||
| + | |||
| + | Ubiquitin-like conjugation by bacterial cGAS enhances anti-phage defence.,Jenson JM, Li T, Du F, Ea CK, Chen ZJ Nature. 2023 Apr;616(7956):326-331. doi: 10.1038/s41586-023-05862-7. Epub 2023 , Feb 27. PMID:36848932<ref>PMID:36848932</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7uq2" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Vs.4 from T4 phage in complex with cGAMP
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