CRISPR-associated Rossmann Fold (CARF) and SMODS-associated and fused to various effector domains (SAVED) are key components of cyclic oligonucleotide-based antiphage signaling systems (CBASS) that sense cyclic oligonucleotides and transmit the signal to an effector inducing cell dormancy or death. Most of the CARFs are components of a CBASS built into type III CRISPR-Cas systems, where the CARF domain binds cyclic oligoA (cOA) synthesized by Cas10 polymerase-cyclase and allosterically activates the effector, typically a promiscuous ribonuclease. Additionally, this signaling pathway includes a ring nuclease, often also a CARF domain (either the sensor itself or a specialized enzyme) that cleaves cOA and mitigates dormancy or death induction. We present a comprehensive census of CARF and SAVED domains in bacteria and archaea, and their sequence- and structure-based classification. There are 10 major families of CARF domains and multiple smaller groups that differ in structural features, association with distinct effectors, and presence or absence of the ring nuclease activity. By comparative genome analysis, we predict specific functions of CARF and SAVED domains and partition the CARF domains into those with both sensor and ring nuclease functions, and sensor-only ones. Several families of ring nucleases functionally associated with sensor-only CARF domains are also predicted.

译文

与CRISPR相关的Rossmann Fold (CARF) 和SMODS相关并融合到各种效应域 (SAVED) 是基于环状寡核苷酸的抗噬菌体信号传导系统 (CBASS) 的关键成分,该系统可感测环状寡核苷酸并将信号传递给诱导细胞休眠或死亡的效应子。大多数CARF是III型CRISPR-Cas系统中内置的cps的组成部分,其中CARF结构域结合由Cas10聚合酶环化酶合成的环状寡核苷酸 (cOA),并通过变构激活效应物,通常是混杂的核糖核酸酶。此外,该信号传导途径包括环核酸酶,通常还包括切割cOA并减轻休眠或死亡诱导的CARF结构域 (传感器本身或专用酶)。我们介绍了细菌和古细菌中CARF和保存域的全面普查,以及它们基于序列和结构的分类。有10个主要的CARF结构域家族和多个较小的基团,它们在结构特征,与不同效应物的关联以及环核酸酶活性的存在与否方面有所不同。通过比较基因组分析,我们预测了CARF和保存的结构域的特定功能,并将CARF结构域划分为具有传感器和环核酸酶功能的结构域,以及仅具有传感器功能的结构域。还预测了与仅传感器CARF结构域功能相关的几个环核酸酶家族。

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