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Cyclic CMP and cyclic UMP mediate bacterial immunity against phages
Cell ( IF 64.5 ) Pub Date : 2021-10-12 , DOI: 10.1016/j.cell.2021.09.031
Nitzan Tal 1 , Benjamin R Morehouse 2 , Adi Millman 1 , Avigail Stokar-Avihail 1 , Carmel Avraham 1 , Taya Fedorenko 1 , Erez Yirmiya 1 , Ehud Herbst 1 , Alexander Brandis 3 , Tevie Mehlman 3 , Yaara Oppenheimer-Shaanan 1 , Alexander F A Keszei 4 , Sichen Shao 4 , Gil Amitai 1 , Philip J Kranzusch 5 , Rotem Sorek 1
Affiliation  

The cyclic pyrimidines 3′,5′-cyclic cytidine monophosphate (cCMP) and 3′,5′-cyclic uridine monophosphate (cUMP) have been reported in multiple organisms and cell types. As opposed to the cyclic nucleotides 3′,5′-cyclic adenosine monophosphate (cAMP) and 3′,5′-cyclic guanosine monophosphate (cGMP), which are second messenger molecules with well-established regulatory roles across all domains of life, the biological role of cyclic pyrimidines has remained unclear. Here we report that cCMP and cUMP are second messengers functioning in bacterial immunity against viruses. We discovered a family of bacterial pyrimidine cyclase enzymes that specifically synthesize cCMP and cUMP following phage infection and demonstrate that these molecules activate immune effectors that execute an antiviral response. A crystal structure of a uridylate cyclase enzyme from this family explains the molecular mechanism of selectivity for pyrimidines as cyclization substrates. Defense systems encoding pyrimidine cyclases, denoted here Pycsar (pyrimidine cyclase system for antiphage resistance), are widespread in prokaryotes. Our results assign clear biological function to cCMP and cUMP as immunity signaling molecules in bacteria.



中文翻译:

环状 CMP 和环状 UMP 介导细菌对噬菌体的免疫

已在多种生物体和细胞类型中报道了环状嘧啶 3',5'-环胞苷一磷酸 (cCMP) 和 3',5'-环尿苷一磷酸 (cUMP)。与环状核苷酸 3',5'-环腺苷一磷酸 (cAMP) 和 3',5'-环鸟苷一磷酸 (cGMP) 不同,它们是第二信使分子,在生命的所有领域都具有良好的调节作用,环状嘧啶的生物学作用仍不清楚。在这里,我们报告 cCMP 和 cUMP 是在细菌对病毒的免疫中起作用的第二信使。我们发现了一个细菌嘧啶环化酶家族,它们在噬菌体感染后特异性合成 cCMP 和 cUMP,并证明这些分子可以激活免疫效应子来执行抗病毒反应。该家族的尿苷酸环化酶的晶体结构解释了嘧啶作为环化底物的选择性分子机制。编码嘧啶环化酶的防御系统,在此表示为 Pycsar(用于抗噬菌体抗性的嘧啶环化酶系统),广泛存在于原核生物中。我们的结果为 cCMP 和 cUMP 作为细菌中的免疫信号分子赋予了明确的生物学功能。

更新日期:2021-11-11
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