Viruses compete with each other for limited cellular resources, and some deliver defense mechanisms that protect the host from competing genetic parasites¹. PARIS is a defense system, often encoded in viral genomes, that is composed of a 55 kDa ABC ATPase (AriA) and a 35 kDa TOPRIM nuclease (AriB)². However, the mechanism by which AriA and AriB function in phage defense is unknown. Here we show that AriA and AriB assemble into a 425 kDa supramolecular immune complex. We use cryo-EM to determine the structure of this complex which explains how six molecules of AriA assemble into a propeller-shaped scaffold that coordinates three subunits of AriB. ATP-dependent detection of foreign proteins triggers the release of AriB, which assembles into a homodimeric nuclease that blocks infection by cleaving host tRNA^Lys. Phage T5 subverts PARIS immunity through expression of a tRNA^Lys variant that is not cleaved by PARIS, and thereby restores viral infection. Collectively, these data explain how AriA functions as an ATP-dependent sensor that detects viral proteins and activates the AriB toxin. PARIS is one of an emerging set of immune systems that form macromolecular complexes for the recognition of foreign proteins, rather than foreign nucleic acids³.

病毒相互竞争有限的细胞资源，有些病毒提供防御机制，保护宿主免受竞争性遗传寄生虫的侵害¹ 。 PARIS 是一种防御系统，通常在病毒基因组中编码，由 55 kDa ABC ATP 酶 (AriA) 和 35 kDa TOPRIM 核酸酶 (AriB) ²组成。然而，AriA 和 AriB 在噬菌体防御中发挥作用的机制尚不清楚。在这里，我们展示了 AriA 和 AriB 组装成 425 kDa 的超分子免疫复合物。我们使用冷冻电镜来确定该复合物的结构，这解释了 AriA 的六个分子如何组装成螺旋桨形支架，该支架协调 AriB 的三个亚基。 ATP 依赖性外源蛋白检测会触发 AriB 的释放，AriB 会组装成同型二聚体核酸酶，通过裂解宿主 tRNA ^Lys来阻止感染。噬菌体 T5 通过表达不被 PARIS 切割的 tRNA ^Lys变体来破坏 PARIS 免疫，从而恢复病毒感染。总的来说，这些数据解释了 AriA 如何作为 ATP 依赖性传感器发挥作用，检测病毒蛋白并激活 AriB 毒素。 PARIS 是一组新兴的免疫系统之一，它形成大分子复合物来识别外来蛋白质，而不是外来核酸³ 。