在病毒感染时用于降解细胞三磷酸腺苷（ATP）的保守免疫效应子家族，这一成果由以色列魏茨曼科学研究所Rotem Sorek、Francois Rousset课题组经过不懈努力而取得。2023年8月17日出版的《细胞》杂志发表了这项成果。
研究人员发现了细菌中的免疫效应子家族，在噬菌体感染时，通过切割腺嘌呤和糖基之间的N-糖苷键来降解细胞三磷酸腺苷和三磷酸脱氧腺苷（dATP）。这些ATP核苷酸酶效应子广泛存在于多种细菌防御系统中，包括基于环寡核苷酸的抗病毒信号系统（CBASS）、原核Argonautes和与核苷酸结合的富含亮氨酸的重复（NLR）样蛋白，研究表明感染期间ATP和dATP的降解能阻止噬菌体繁殖。
通过分析免疫ATP核苷酸酶结构域的同系物，研究人员发现并表征了Detocs，这是一个具有双组分磷酸转移信号结构的细菌防御系统家族。免疫ATP核苷酸酶结构域也存在于具有免疫样结构的不同真核蛋白中，研究人员在生化水平证明了真核同系物保留了ATP核苷酸酶活性。该研究结果表明，ATP和dATP降解是一种细胞自主的先天免疫策略。
研究人员表示，在病毒感染期间，细胞可以部署免疫策略剥夺病毒复制所必需的分子。
附：英文原文
Title: A conserved family of immune effectors cleaves cellular ATP upon viral infection
Author: Francois Rousset, Erez Yirmiya, Shahar Nesher, Alexander Brandis, Tevie Mehlman, Maxim Itkin, Sergey Malitsky, Adi Millman, Sarah Melamed, Rotem Sorek
Issue&Volume: 2023/08/17
Abstract: During viral infection, cells can deploy immune strategies that deprive viruses ofmolecules essential for their replication. Here, we report a family of immune effectorsin bacteria that, upon phage infection, degrade cellular adenosine triphosphate (ATP)and deoxyadenosine triphosphate (dATP) by cleaving the N-glycosidic bond between theadenine and sugar moieties. These ATP nucleosidase effectors are widely distributedwithin multiple bacterial defense systems, including cyclic oligonucleotide-basedantiviral signaling systems (CBASS), prokaryotic argonautes, and nucleotide-bindingleucine-rich repeat (NLR)-like proteins, and we show that ATP and dATP degradationduring infection halts phage propagation. By analyzing homologs of the immune ATPnucleosidase domain, we discover and characterize Detocs, a family of bacterial defensesystems with a two-component phosphotransfer-signaling architecture. The immune ATPnucleosidase domain is also encoded within diverse eukaryotic proteins with immune-likearchitectures, and we show biochemically that eukaryotic homologs preserve the ATPnucleosidase activity. Our findings suggest that ATP and dATP degradation is a cell-autonomousinnate immune strategy conserved across the tree of life.
DOI: 10.1016/j.cell.2023.07.020
Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00797-3