8h39: Difference between revisions
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==Structure of Acb2 complexed with c-di-AMP== | |||
<StructureSection load='8h39' size='340' side='right'caption='[[8h39]], [[Resolution|resolution]] 2.01Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8h39]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_phage_PaP2 Pseudomonas phage PaP2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8H39 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8H39 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2BA:(2R,3R,3AS,5R,7AR,9R,10R,10AS,12R,14AR)-2,9-BIS(6-AMINO-9H-PURIN-9-YL)OCTAHYDRO-2H,7H-DIFURO[3,2-D 3,2-J][1,3,7,9,2,8]TETRAOXADIPHOSPHACYCLODODECINE-3,5,10,12-TETROL+5,12-DIOXIDE'>2BA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=8h39 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8h39 OCA], [https://pdbe.org/8h39 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8h39 RCSB], [https://www.ebi.ac.uk/pdbsum/8h39 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8h39 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q6PVL0_9CAUD Q6PVL0_9CAUD] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
A fundamental strategy of eukaryotic antiviral immunity involves the cGAS enzyme, which synthesizes 2',3'-cGAMP and activates the effector STING. Diverse bacteria contain cGAS-like enzymes that produce cyclic oligonucleotides and induce anti-phage activity, known as CBASS. However, this activity has only been demonstrated through heterologous expression. Whether bacteria harboring CBASS antagonize and co-evolve with phages is unknown. Here, we identified an endogenous cGAS-like enzyme in Pseudomonas aeruginosa that generates 3',3'-cGAMP during phage infection, signals to a phospholipase effector, and limits phage replication. In response, phages express an anti-CBASS protein ("Acb2") that forms a hexamer with three 3',3'-cGAMP molecules and reduces phospholipase activity. Acb2 also binds to molecules produced by other bacterial cGAS-like enzymes (3',3'-cUU/UA/UG/AA) and mammalian cGAS (2',3'-cGAMP), suggesting broad inhibition of cGAS-based immunity. Upon Acb2 deletion, CBASS blocks lytic phage replication and lysogenic induction, but rare phages evade CBASS through major capsid gene mutations. Altogether, we demonstrate endogenous CBASS anti-phage function and strategies of CBASS inhibition and evasion. | |||
Bacteriophages inhibit and evade cGAS-like immune function in bacteria.,Huiting E, Cao X, Ren J, Athukoralage JS, Luo Z, Silas S, An N, Carion H, Zhou Y, Fraser JS, Feng Y, Bondy-Denomy J Cell. 2023 Jan 31:S0092-8674(22)01584-7. doi: 10.1016/j.cell.2022.12.041. PMID:36750095<ref>PMID:36750095</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8h39" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Pseudomonas phage PaP2]] | |||
[[Category: Cao XL]] | |||
[[Category: Feng Y]] | |||
Revision as of 15:47, 22 February 2023
Structure of Acb2 complexed with c-di-AMPStructure of Acb2 complexed with c-di-AMP
Structural highlights
FunctionPublication Abstract from PubMedA fundamental strategy of eukaryotic antiviral immunity involves the cGAS enzyme, which synthesizes 2',3'-cGAMP and activates the effector STING. Diverse bacteria contain cGAS-like enzymes that produce cyclic oligonucleotides and induce anti-phage activity, known as CBASS. However, this activity has only been demonstrated through heterologous expression. Whether bacteria harboring CBASS antagonize and co-evolve with phages is unknown. Here, we identified an endogenous cGAS-like enzyme in Pseudomonas aeruginosa that generates 3',3'-cGAMP during phage infection, signals to a phospholipase effector, and limits phage replication. In response, phages express an anti-CBASS protein ("Acb2") that forms a hexamer with three 3',3'-cGAMP molecules and reduces phospholipase activity. Acb2 also binds to molecules produced by other bacterial cGAS-like enzymes (3',3'-cUU/UA/UG/AA) and mammalian cGAS (2',3'-cGAMP), suggesting broad inhibition of cGAS-based immunity. Upon Acb2 deletion, CBASS blocks lytic phage replication and lysogenic induction, but rare phages evade CBASS through major capsid gene mutations. Altogether, we demonstrate endogenous CBASS anti-phage function and strategies of CBASS inhibition and evasion. Bacteriophages inhibit and evade cGAS-like immune function in bacteria.,Huiting E, Cao X, Ren J, Athukoralage JS, Luo Z, Silas S, An N, Carion H, Zhou Y, Fraser JS, Feng Y, Bondy-Denomy J Cell. 2023 Jan 31:S0092-8674(22)01584-7. doi: 10.1016/j.cell.2022.12.041. PMID:36750095[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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