Deazaguanylation is a nucleobase-protein conjugation required for type IV CBASS immunity
2025-09-25
7-Deazapurines are nucleobase analogs essential for nucleic acid modifications in nearly all cellular life. In this study, we discovered a role for 7-deazapurines in protein modification within type IV cyclic oligonucleotide–based antiviral signaling system (CBASS) antiphage defense and defined functions for CBASS ancillary proteins Cap9 and Cap10 in nucleobase-protein conjugation. A structure of Cap10 revealed a transfer RNA transglycosylase family enzyme remodeled to bind a partner cGAS/DncV–like nucleotidyltransferase that is modified with an N-terminal 7-amido-7-deazaguanine (NDG) nucleobase. A structure of Cap9 explained how this QueC-like enzyme co-opts a 7-deazapurine biosynthetic reaction to install NDG. We show that Cap9, Cap10, and protein deazaguanylation are essential for host defense against phage infection. Our results define a 7-deazapurine protein modification and explain how nucleobase biosynthetic machinery has been repurposed for antiviral immunity.