Inhibition of Type III CRISPR-Cas Immunity by an Archaeal Virus-Encoded Anti-CRISPR Protein
Inhibition of Type III CRISPR-Cas Immunity by an Archaeal Virus-Encoded Anti-CRISPR Protein
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DOI：
10.1016/j.cell.2019.09.003
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发表时间：
2019-10-03
期刊：
影响因子：
64.5
通讯作者：
Peng, Xu
中科院分区：
文献类型：
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作者：
Bhoobalan-Chitty, Yuvaraj;Johansen, Thomas Baek;Peng, Xu
细菌和古细菌拥有惊人的CRISPR-Cas系统多样性，分为六种类型，对病毒感染构成了重要的屏障。作为病毒-宿主军备竞赛的一部分，病毒编码I型、II型和V型CRISPR-Cas系统的蛋白质抑制剂，但是否存在其他机制不同的CRI - R-Cas类型的天然抑制剂尚不清楚。在这里，我们发现了一种III型CRISPR-Cas抑制剂，由Sulfolobus病毒SIRV2编码的AcrIIIB1。AcrIIIB1专一抑制由辅助蛋白Csx1的RNase活性介导的CRISPR-Cas亚型III-B免疫。AcrIIIB1似乎不与Csx1结合，而是与两种不同的亚型III-B效应复合物（cmr - α和cmr - γ）相互作用，这两种复合物在响应原间隔物转录物结合时，已知会合成激活Csx1“侧链”RNase的环寡腺苷酸（cOAs）。综上所述，我们推断AcrIIIB1通过干扰Csx1 rnase相关过程抑制HI-B型CRISPR-Cas免疫。
Bacteria and archaea possess a striking diversity of CRISPR-Cas systems divided into six types, posing a significant barrier to viral infection. As part of the virus-host arms race, viruses encode protein inhibitors of type I, II, and V CRISPR-Cas systems, but whether there are natural inhibitors of the other, mechanistically distinct CRI - R-Cas types is unknown. Here, we present the discovery of a type III CRISPR-Cas inhibitor, AcrIIIB1, encoded by the Sulfolobus virus SIRV2. AcrIIIB1 exclusively inhibits CRISPR-Cas subtype III-B immunity mediated by the RNase activity of the accessory protein Csx1. AcrIIIB1 does not appear to bind Csx1 but, rather, interacts with two distinct subtype III-B effector complexes-Cmr-alpha and Cmr-gamma-which, in response to protospacer transcript binding, are known to synthesize cyclic oligoadenylates (cOAs) that activate the Csx1 "collateral" RNase. Taken together, we infer that AcrIIIB1 inhibits type HI-B CRISPR-Cas immunity by interfering with a Csx1 RNase-related process.