Cyclic CMP and cyclic UMP mediate bacterial immunity against phages.
Cyclic CMP and cyclic UMP mediate bacterial immunity against phages.
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DOI：
10.1016/j.cell.2021.09.031
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发表时间：
2021-11-11
期刊：
影响因子：
64.5
通讯作者：
Sorek, Rotem
中科院分区：
文献类型：
--
作者：
Tal, Nitzan;Morehouse, Benjamin R.;Millman, Adi;Stokar-Avihail, Avigail;Avraham, Carmel;Fedorenko, Taya;Yirmiya, Erez;Herbst, Ehud;Brandis, Alexander;Mehlman, Tevie;Oppenheimer-Shaanan, Yaara;Keszei, Alexander F. A.;Shao, Sichen;Amitai, Gil;Kranzusch, Philip J.;Sorek, Rotem
环嘧啶cCMP和cUMP已在多种生物和细胞类型中被报道。与环核苷酸cAMP和cGMP相反，环嘧啶的生物学作用尚不清楚，cAMP和cGMP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。在这里，我们报道cCMP和cUMP是第二信使，在细菌对病毒的免疫中起作用。我们发现了一个细菌嘧啶环化酶家族，在噬菌体感染后特异性合成cCMP和cUMP，并证明这些分子激活执行抗病毒反应的免疫效应物。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的分子机制。编码嘧啶环化酶的防御系统在原核生物中广泛存在，这里用Pycsar表示嘧啶环化酶系统的抗噬菌体抗性。我们的研究结果明确了cCMP和cUMP作为细菌免疫信号分子的生物学功能。
The cyclic pyrimidines cCMP and cUMP have been reported in multiple organisms and cell types. As opposed to the cyclic nucleotides cAMP and cGMP, which are second messenger molecules with well-established regulatory roles across all domains of life, the biological role of cyclic pyrimidines 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” for Pyrimidine Cyclase Systems for Antiphage Resistance, are widespread in prokaryotes. Our results assign clear biological function to cCMP and cUMP as immunity signaling molecules in bacteria.
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影响因子：
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通讯作者：
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
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通讯作者：
Cowtan, K