Structural insights into mechanisms of Argonaute protein-associated NADase activation in bacterial immunity.

ABSTRACT: Nicotinamide adenine dinucleotide (NAD⁺) is a central metabolite in cellular processes. Depletion of NAD⁺ has been demonstrated to be a prevalent theme in both prokaryotic and eukaryotic immune responses. Short prokaryotic Argonaute proteins (Agos) are associated with NADase domain-containing proteins (TIR-APAZ or SIR2-APAZ) encoded in the same operon. They confer immunity against mobile genetic elements, such as bacteriophages and plasmids, by inducing NAD⁺ depletion upon recognition of target nucleic acids. However, the molecular mechanisms underlying the activation of such prokaryotic NADase/Ago immune systems remain unknown. Here, we report multiple cryo-EM structures of NADase/Ago complexes from two distinct systems (TIR-APAZ/Ago and SIR2-APAZ/Ago). Ta

SUBMITTER: Wang X 

PROVIDER: S-EPMC10474274 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature