Structural basis of ssDNA-guided NADase activation of prokaryotic SPARTA system.

ABSTRACT: Short prokaryotic Argonaute and the associated TIR-APAZ (SPARTA) proteins constitute a prokaryotic immune system, mediating RNA- or DNA-guided target single-stranded DNA (ssDNA) to activate NADase activity and induce cell death by degrading NAD+ in response to invading plasmids. Although the guide RNA-mediated targeting mechanism of SPARTA has been established, the functional role and mechanisms of guide DNA-mediated SPARTA remain poorly understood. Here, we report two crystal structures of Crenotalea thermophila SPARTA complexes with 5'-phosphorylated 21-nt guide DNA and complementary target ssDNA lengths of 15 or 20 nt. The structures demonstrate specific recognition of the 5'-OH or 3'-OH groups in target DNA by SPARTA, while not recognizing the 5'-P group in guide DNA. This suggests dis

SUBMITTER: Hu R 

PROVIDER: S-EPMC11851103 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature