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环CMP和环UMP介导细菌对噬菌体的免疫
作者:小柯机器人 发布时间:2021/10/17 19:31:02

以色列魏茨曼科学研究所Rotem Sorek、美国哈佛大学Philip J. Kranzusch等研究人员合作发现,环CMP和环UMP介导细菌对噬菌体的免疫。2021年10月12日,国际知名学术期刊《细胞》在线发表了这一成果。

研究人员表示,环嘧啶3′,5′-环胞苷单磷酸(cCMP)和3′,5′-环尿苷单磷酸(cUMP)已在多种生物体和细胞类型中被报道。环核苷酸3′,5′-环腺苷单磷酸(cAMP)和3′,5′-环鸟苷单磷酸(cGMP)是第二信使分子,在所有的生命领域都有公认的调节作用,与之相反,环嘧啶的生物学作用仍然不清楚。

研究人员发现,cCMP和cUMP是在细菌对病毒的免疫中发挥作用的第二信使。研究人员发现了一个细菌嘧啶环化酶家族,它们在噬菌体感染后专门合成cCMP和cUMP,并证明这些分子激活了执行抗病毒反应的免疫效应器。该家族的一种尿苷酸环化酶的晶体结构解释了对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,表示为Pycsar(抗噬菌体的嘧啶环化酶系统),在原核生物中广泛存在。这项研究结果赋予了cCMP和cUMP作为细菌免疫信号分子的明确生物功能。

附:英文原文

Title: Cyclic CMP and cyclic UMP mediate bacterial immunity against phages

Author: Nitzan Tal, Benjamin R. Morehouse, Adi Millman, Avigail Stokar-Avihail, Carmel Avraham, Taya Fedorenko, Erez Yirmiya, Ehud Herbst, Alexander Brandis, Tevie Mehlman, Yaara Oppenheimer-Shaanan, Alexander F.A. Keszei, Sichen Shao, Gil Amitai, Philip J. Kranzusch, Rotem Sorek

Issue&Volume: 2021-10-12

Abstract: The cyclic pyrimidines 3′,5′-cyclic cytidine monophosphate (cCMP) and 3′,5′-cyclicuridine monophosphate (cUMP) have been reported in multiple organisms and cell types.As opposed to the cyclic nucleotides 3′,5′-cyclic adenosine monophosphate (cAMP) and3′,5′-cyclic guanosine monophosphate (cGMP), which are second messenger moleculeswith well-established regulatory roles across all domains of life, the biologicalrole of cyclic pyrimidines has remained unclear. Here we report that cCMP and cUMPare second messengers functioning in bacterial immunity against viruses. We discovereda family of bacterial pyrimidine cyclase enzymes that specifically synthesize cCMPand cUMP following phage infection and demonstrate that these molecules activate immuneeffectors that execute an antiviral response. A crystal structure of a uridylate cyclaseenzyme from this family explains the molecular mechanism of selectivity for pyrimidinesas cyclization substrates. Defense systems encoding pyrimidine cyclases, denoted herePycsar (pyrimidine cyclase system for antiphage resistance), are widespread in prokaryotes.Our results assign clear biological function to cCMP and cUMP as immunity signalingmolecules in bacteria.

DOI: 10.1016/j.cell.2021.09.031

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)01114-4

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/