Structural characterization of macro domain-containing Thoeris antiphage defense systems.

ABSTRACT: Thoeris defense systems protect bacteria from infection by phages via abortive infection. In these systems, ThsB proteins serve as sensors of infection and generate signaling nucleotides that activate ThsA effectors. Silent information regulator and SMF/DprA-LOG (SIR2-SLOG) containing ThsA effectors are activated by cyclic ADP-ribose (ADPR) isomers 2'cADPR and 3'cADPR, triggering abortive infection via nicotinamide adenine dinucleotide (NAD⁺) depletion. Here, we characterize Thoeris systems with transmembrane and macro domain (TM-macro)-containing ThsA effectors. We demonstrate that ThsA macro domains bind ADPR and imidazole adenine dinucleotide (IAD), but not 2'cADPR or 3'cADPR. Combining crystallography, in silico predictions, and site-directed mutagenesis, we show that ThsA m

SUBMITTER: Shi Y 

PROVIDER: S-EPMC11204291 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature