Single phage proteins sequester TIR- and cGAS-generated signaling molecules.

ABSTRACT: Prokaryotic anti-phage immune systems use TIR (toll/interleukin-1 receptor) and cGAS (cyclic GMP-AMP synthase) enzymes to produce 1"-3'/1"-2' glycocyclic ADPR (gcADPR) and cyclid di-/trinucleotides (CDNs and CTNs) signaling molecules that limit phage replication, respectively ^1-3. However, how phages neutralize these common systems is largely unknown. Here, we show that Thoeris anti-defense proteins Tad1 ⁴ and Tad2 ⁵ both have anti-CBASS activity by simultaneously sequestering CBASS cyclic oligonucleotides. Strikingly, apart from binding Thoeris signals 1"-3' and 1"-2' gcADPR, Tad1 also binds numerous CBASS CDNs/CTNs with high affinity, inhibiting CBASS systems using these molecules in vivo and in vitro. The hexameric Tad1 has six binding site

SUBMITTER: Li D 

PROVIDER: S-EPMC10680739 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature