Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
Cell. 2023 Aug 17;186(17):3619-3631.e13. doi: 10.1016/j.cell.2023.07.020.
During viral infection, cells can deploy immune strategies that deprive viruses of molecules essential for their replication. Here, we report a family of immune effectors in bacteria that, upon phage infection, degrade cellular adenosine triphosphate (ATP) and deoxyadenosine triphosphate (dATP) by cleaving the N-glycosidic bond between the adenine and sugar moieties. These ATP nucleosidase effectors are widely distributed within multiple bacterial defense systems, including cyclic oligonucleotide-based antiviral signaling systems (CBASS), prokaryotic argonautes, and nucleotide-binding leucine-rich repeat (NLR)-like proteins, and we show that ATP and dATP degradation during infection halts phage propagation. By analyzing homologs of the immune ATP nucleosidase domain, we discover and characterize Detocs, a family of bacterial defense systems with a two-component phosphotransfer-signaling architecture. The immune ATP nucleosidase domain is also encoded within diverse eukaryotic proteins with immune-like architectures, and we show biochemically that eukaryotic homologs preserve the ATP nucleosidase activity. Our findings suggest that ATP and dATP degradation is a cell-autonomous innate immune strategy conserved across the tree of life.
在病毒感染过程中，细胞可以利用免疫策略剥夺病毒复制所必需的分子。在这里，我们报道了一类存在于细菌中的免疫效应因子，当噬菌体感染时，这些效应因子通过切割腺嘌呤和糖部分之间的 N-糖苷键来降解细胞三磷酸腺苷 (ATP) 和脱氧三磷酸腺苷 (dATP)。这些 ATP 核苷酶效应因子广泛分布于多种细菌防御系统中，包括基于环状寡核苷酸的抗病毒信号系统 (CBASS)、原核 Argonautes 和核苷酸结合富含亮氨酸重复 (NLR) 样蛋白，我们表明感染过程中 ATP 和 dATP 的降解会阻止噬菌体的繁殖。通过分析免疫 ATP 核苷酶结构域的同源物，我们发现并表征了 Detocs，这是一类具有双组分磷酸转移信号结构的细菌防御系统。免疫 ATP 核苷酶结构域也编码在具有免疫样结构的各种真核蛋白中，我们通过生化实验表明真核同源物保留了 ATP 核苷酶活性。我们的研究结果表明，ATP 和 dATP 的降解是一种在整个生命之树上保守的细胞自主先天免疫策略。
