Phage anti-CBASS protein simultaneously sequesters cyclic trinucleotides and dinucleotides.

ABSTRACT: CBASS is a common anti-phage immune system that uses cyclic oligonucleotide signals to activate effectors and limit phage replication. In turn, phages encode anti-CBASS (Acb) proteins. We recently uncovered a widespread phage anti-CBASS protein Acb2 that acts as a "sponge" by forming a hexamer complex with three cGAMP molecules. Here, we identified that Acb2 binds and sequesters many CBASS and cGAS-produced cyclic dinucleotides in vitro and inhibits cGAMP-mediated STING activity in human cells. Surprisingly, Acb2 also binds CBASS cyclic trinucleotides 3'3'3'-cyclic AMP-AMP-AMP (cA₃) and 3'3'3'-cAAG with high affinity. Structural characterization identified a distinct binding pocket within the Acb2 hexamer that binds two cyclic trinucleotide molecules and another binding p

SUBMITTER: Cao X 

PROVIDER: S-EPMC10312549 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature