8H39

Structure of Acb2 complexed with c-di-AMP

Summary for 8H39

• Entry DOI: 10.2210/pdb8h39/pdb
• Descriptor: p26, (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, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: inhibitor, complex, viral protein
• Biological source: Pseudomonas phage PaP2
• Total number of polymer chains: 6
• Total formula weight: 67421.06

Authors

Feng, Y.,Cao, X.L. (deposition date: 2022-10-08, release date: 2023-02-22, Last modification date: 2024-04-03)

Primary citation

Huiting, E.,Cao, X.,Ren, J.,Athukoralage, J.S.,Luo, Z.,Silas, S.,An, N.,Carion, H.,Zhou, Y.,Fraser, J.S.,Feng, Y.,Bondy-Denomy, J.
Bacteriophages inhibit and evade cGAS-like immune function in bacteria.
Cell, 186:864-, 2023

PubMed Abstract: 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.

PubMed: 36750095
DOI: 10.1016/j.cell.2022.12.041

Experimental method

X-RAY DIFFRACTION (2.01 Å)