9NTO

Structure of Cap9-CdnD complex containing NDG modification

Summary for 9NTO

• Entry DOI: 10.2210/pdb9nto/pdb
• Descriptor: CdnD, Cap9, ADENOSINE MONOPHOSPHATE, ... (7 entities in total)
• Functional Keywords: cd-ntase, quec, cbass, antiviral protein
• Biological source: Hyphomicrobiales; More
• Total number of polymer chains: 2
• Total formula weight: 55370.81

Authors

Wassarman, D.R.,Pfaff, P.,Paulo, J.A.,Gygi, S.P.,Shokat, K.M.,Kranzusch, P.J. (deposition date: 2025-03-18, release date: 2025-05-07, Last modification date: 2025-10-08)

Primary citation

Wassarman, D.R.,Pfaff, P.,Paulo, J.A.,Gygi, S.P.,Shokat, K.M.,Kranzusch, P.J.
Deazaguanylation is a nucleobase-protein conjugation required for type IV CBASS immunity.
Science, 389:1347-1352, 2025

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.

PubMed: 40997174
DOI: 10.1126/science.adx6053

Experimental method

X-RAY DIFFRACTION (2.15 Å)