Structure and Mechanism of a Cyclic Trinucleotide-Activated Bacterial Endonuclease Mediating Bacteriophage Immunity
Structure and Mechanism of a Cyclic Trinucleotide-Activated Bacterial Endonuclease Mediating Bacteriophage Immunity
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DOI：
10.1016/j.molcel.2019.12.010
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发表时间：
2020-02-20
期刊：
影响因子：
16
通讯作者：
Corbett, Kevin D.
中科院分区：
文献类型：
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作者：
Lau, Rebecca K.;Ye, Qiaozhen;Corbett, Kevin D.
细菌对外来入侵者拥有一系列防御系统，包括一个广泛分布的噬菌体防御系统，称为CBASS(基于环寡核苷酸的抗噬菌体信号系统)。在CBASS系统中，cGAS/DncV样核苷酸转移酶合成环状二核苷酸或三核苷酸第二信使，这些分子激活不同的效应器，通过流产感染介导噬菌体免疫。在这里，我们证明CBass效应器NucC与限制性内切酶有关，但唯一地组装成同源三聚体。NucC三聚体与环状三腺苷第二信使的结合促进了NucC高六聚体的组装，该NucC高六聚体能够切割非特异性双链DNA。在受感染的细胞中，NucC的激活导致细菌染色体的完全破坏，导致细胞在完成噬菌体复制之前死亡。除了CBASS系统外，我们还在30多个III型CRISPR/CAS系统中发现了NucC同系物，它们可能是由这些系统的效应器合成的环寡腺苷第二信使激活的辅助核酸酶
Bacteria possess an array of defenses against foreign invaders, including a broadly distributed bacteriophage defense system termed CBASS (cyclic oligonucleotide-based anti-phage signaling system). In CBASS systems, a cGAS/DncV-like nucleotidyltransferase synthesizes cyclic di- or tri-nucleotide second messengers in response to infection, and these molecules activate diverse effectors to mediate bacteriophage immunity via abortive infection. Here, we show that the CBASS effector NucC is related to restriction enzymes but uniquely assembles into a homotrimer. Binding of NucC trimers to a cyclic tri-adenylate second messenger promotes assembly of a NucC homohexamer competent for non-specific double-strand DNA cleavage. In infected cells, NucC activation leads to complete destruction of the bacterial chromosome, causing cell death prior to completion of phage replication. In addition to CBASS systems, we identify NucC homologs in over 30 type III CRISPR/Cas systems, where they likely function as accessory nucleases activated by cyclic oligoadenylate second messengers synthesized by these systems' effector