脱氮酰化是IV型CBASS免疫所需的核碱基-蛋白偶联

IF 45.8 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2025-09-25 DOI:10.1126/science.adx6053

Douglas R. Wassarman, Patrick Pfaff, Joao A. Paulo, Steven P. Gygi, Kevan M. Shokat, Philip J. Kranzusch

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引用次数: 0

摘要

7-去氮嘌呤是几乎所有细胞生命中核酸修饰所必需的核碱基类似物。在这项研究中，我们发现了7-去氮嘌呤在IV型环寡核苷酸抗病毒信号系统（CBASS）抗噬菌体防御中的蛋白修饰作用，并确定了CBASS辅助蛋白Cap9和Cap10在核碱基-蛋白偶联中的功能。Cap10的结构揭示了一个转移RNA转糖基酶家族酶，该酶被改造成与一个n端7-氨基-7-去氮鸟嘌呤（NDG）核碱基修饰的伙伴cGAS/ dncv样核苷酸转移酶结合。Cap9的结构解释了这种类似quc的酶如何选择7-去氮杂嘌呤生物合成反应来安装NDG。我们发现Cap9， Cap10和蛋白脱氮酰化对于宿主防御噬菌体感染至关重要。我们的研究结果定义了一种7-去氮杂嘌呤蛋白修饰，并解释了核碱基生物合成机制如何被重新用于抗病毒免疫。

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

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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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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