8h2x: Difference between revisions
New page: '''Unreleased structure''' The entry 8h2x is ON HOLD Authors: Description: Category: Unreleased Structures |
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==Structure of Acb2== | |||
<StructureSection load='8h2x' size='340' side='right'caption='[[8h2x]], [[Resolution|resolution]] 2.69Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8h2x]] 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=8H2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8H2X FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.69Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=8h2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8h2x OCA], [https://pdbe.org/8h2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8h2x RCSB], [https://www.ebi.ac.uk/pdbsum/8h2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8h2x ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ACB2_BPPP3 ACB2_BPPP3] Antagonizes CBASS (cyclic oligonucleotide-based antiphage signaling system) (PubMed:36750095). Binds and sequesters host-produced 3',3'-cyclic GMP-AMP (cGAMP) with a dissociation constant of about 87 nM; each homohexamer binds 3 cGAMP molecules with 1 cGAMP molecule binding to 2 monomers (PubMed:36750095). Sequestration of cGAMP inhibits the cGAMP-activated phospholipase activity of host CBASS effector protein CapV (PubMed:36750095). Does not degrade the cyclic nucleotide (PubMed:36750095). Also binds other cyclic dinucleotides including; 2',3'-cyclic GMP-AMP, cyclic-di-AMP, c-di-UMP and c-UMP-AMP with high affinity, only weakly to c-UMP-GMP and not to cyclic-di-GMP (PubMed:36750095). Also antagonizes the effector protein of P.aeruginosa type I-A and type I-B CBASS systems (capV in ATCC 33351 and a membrane protein in strain JD332 respectively) (PubMed:36750095).<ref>PMID:36750095</ref> | |||
<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 Feb 16;186(4):864-876.e21. doi: 10.1016/j.cell.2022.12.041. Epub 2023 , Feb 6. 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 8h2x" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Pseudomonas phage PaP2]] | |||
[[Category: Cao XL]] | |||
[[Category: Feng Y]] | |||
Latest revision as of 22:50, 29 May 2024
Structure of Acb2Structure of Acb2
Structural highlights
FunctionACB2_BPPP3 Antagonizes CBASS (cyclic oligonucleotide-based antiphage signaling system) (PubMed:36750095). Binds and sequesters host-produced 3',3'-cyclic GMP-AMP (cGAMP) with a dissociation constant of about 87 nM; each homohexamer binds 3 cGAMP molecules with 1 cGAMP molecule binding to 2 monomers (PubMed:36750095). Sequestration of cGAMP inhibits the cGAMP-activated phospholipase activity of host CBASS effector protein CapV (PubMed:36750095). Does not degrade the cyclic nucleotide (PubMed:36750095). Also binds other cyclic dinucleotides including; 2',3'-cyclic GMP-AMP, cyclic-di-AMP, c-di-UMP and c-UMP-AMP with high affinity, only weakly to c-UMP-GMP and not to cyclic-di-GMP (PubMed:36750095). Also antagonizes the effector protein of P.aeruginosa type I-A and type I-B CBASS systems (capV in ATCC 33351 and a membrane protein in strain JD332 respectively) (PubMed:36750095).[1] Publication 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 Feb 16;186(4):864-876.e21. doi: 10.1016/j.cell.2022.12.041. Epub 2023 , Feb 6. PMID:36750095[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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