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

• 成果类型: Article
• 署名作者: Wassarman, Douglas R.; Pfaff, Patrick; Paulo, Joao A.; Gygi, Steven P.; Shokat, Kevan M.; Kranzusch, Philip J.
• 署名单位: Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Howard Hughes Medical Institute; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13949
• DOI: 10.1126/science.adx6053
• 发表日期: 2025-09-25
• 页码: 1347-1352
• 关键词: multiple sequence alignment; transfer-rna; crystal-structure; biosynthetic-pathway; nucleoside q; mechanism; queuine; base; quec

摘要

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.