9NTO | pdb_00009nto

Deazaguanylation is a nucleobase-protein conjugation required for type IV CBASS immunity.

(2025) Science 389: 1347-1352

• PubMed: 40997174 Search on PubMed
• DOI: https://doi.org/10.1126/science.adx6053
• Primary Citation of Related Structures:  
  9NTN, 9NTO


• PubMed Abstract: 
  

  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.

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Organizational Affiliation: 
• Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Cellular and Molecular Pharmacology and Howard Hughes Medical Institute, University of California, San Francisco, CA, USA.
Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Parker Institute for Cancer Immunotherapy at Dana-Farber Cancer Institute, Boston, MA, USA.
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