Nucleotide-activated effector deployment, prototyped by interferon-dependent immunity, is a common mechanistic theme shared by immune systems of several animals and prokaryotes. Prokaryotic versions include CRISPR-Cas with the CRISPR polymerase domain, their minimal variants, and systems with second messenger oligonucleotide or dinucleotide synthetase (SMODS). Cyclic or linear oligonucleotide signals in these systems help set a threshold for the activation of potentially deleterious downstream effectors in response to invader detection. We establish such a regulatory mechanism to be a more general principle of immune systems, which can also operate independently of such messengers. Using sensitive sequence analysis and comparative genomics, we identify 12 new prokaryotic immune systems, which we unify by this principle of threshold-dependent effector activation. These display regulatory mechanisms paralleling physiological signaling based on 3′-5′ cyclic mononucleotides, NAD⁺-derived messengers, two- and one-component signaling that includes histidine kinase-based signaling, and proteolytic activation. Furthermore, these systems allowed the identification of multiple new sensory signal sensory components, such as a tetratricopeptide repeat (TPR) scaffold predicted to recognize NAD⁺-derived signals, unreported versions of the STING domain, prokaryotic YEATS domains, and a predicted nucleotide sensor related to receiver domains. We also identify previously unrecognized invader detection components and effector components, such as prokaryotic versions of the Wnt domain. Finally, we show that there have been multiple acquisitions of unidentified STING domains in eukaryotes, while the TPR scaffold was incorporated into the animal immunity/apoptosis signal-regulating kinase (ASK) signalosome.

中文翻译：

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鉴定原核免疫系统未表征的成分及其各种真核再形成。

核苷酸激活的效应物的部署，是由干扰素依赖性免疫产生的，是几种动物和原核生物的免疫系统共有的一个常见的机制主题。原核生物版本包括具有CRISPR聚合酶结构域的CRISPR-Cas，其最小变异体以及具有第二信使寡核苷酸或二核苷酸合成酶（SMODS）的系统。这些系统中的环状或线性寡核苷酸信号有助于设定阈值，以响应入侵者的检测激活潜在有害的下游效应子。我们将这种调节机制确立为免疫系统的更普遍原理，它也可以独立于此类信使运行。使用敏感的序列分析和比较基因组学，我们确定了12种新的原核免疫系统，我们通过依赖阈值的效应子激活这一原理来统一这一点。这些显示调节机制与基于3'-5'环状单核苷酸NAD的生理信号平行⁺衍生的信使，包括基于组氨酸激酶的信号传导的二成分和一成分信号传导以及蛋白水解激活。此外，这些系统还可以识别多个新的感觉信号感觉成分，例如预测可识别NAD ⁺的四肽重复（TPR）支架。衍生信号，STING域的未报告版本，YEATS原核域以及与受体域相关的预测核苷酸传感器。我们还将识别以前无法识别的入侵者检测组件和效应器组件，例如Wnt域的原核版本。最后，我们显示，在真核生物中已经获得了多个未知STING结构域，而TPR支架被并入了动物免疫/细胞凋亡信号调节激酶（ASK）信号小体中。