Cell ( IF 64.5 ) Pub Date : 2023-02-09 , DOI: 10.1016/j.cell.2023.01.026 Yina Gao 1 , Xiu Luo 1 , Peipei Li 2 , Zhaolong Li 2 , Feng Ye 3 , Songqing Liu 1 , Pu Gao 2
Adenosine-to-inosine RNA editing has been proposed to be involved in a bacterial anti-phage defense system called RADAR. RADAR contains an adenosine triphosphatase (RdrA) and an adenosine deaminase (RdrB). Here, we report cryo-EM structures of RdrA, RdrB, and currently identified RdrA-RdrB complexes in the presence or absence of RNA and ATP. RdrB assembles into a dodecameric cage with catalytic pockets facing outward, while RdrA adopts both autoinhibited tetradecameric and activation-competent heptameric rings. Structural and functional data suggest a model in which RNA is loaded through the bottom section of the RdrA ring and translocated along its inner channel, a process likely coupled with ATP-binding status. Intriguingly, up to twelve RdrA rings can dock one RdrB cage with precise alignments between deaminase catalytic pockets and RNA-translocation channels, indicative of enzymatic coupling of RNA translocation and deamination. Our data uncover an interesting mechanism of enzymatic coupling and anti-phage defense through supramolecular assemblies.
中文翻译:
RADAR 抗噬菌体超分子组装体的分子基础
腺苷到肌苷 RNA 编辑已被提议参与称为 RADAR 的细菌抗噬菌体防御系统。RADAR 包含一种腺苷三磷酸酶 (RdrA) 和一种腺苷脱氨酶 (RdrB)。在这里,我们报告了 RdrA、RdrB 的冷冻电镜结构,以及目前在存在或不存在 RNA 和 ATP 的情况下鉴定的 RdrA-RdrB 复合物。RdrB 组装成一个十二聚体笼,催化口袋朝外,而 RdrA 采用自抑制的十四聚体和具有活化能力的七聚体环。结构和功能数据表明一个模型,其中 RNA 通过 RdrA 环的底部加载并沿其内部通道转移,这一过程可能与 ATP 结合状态相结合。有趣的是,多达 12 个 RdrA 环可以停靠一个 RdrB 笼,脱氨酶催化口袋和 RNA 易位通道之间精确对齐,表明 RNA 易位和脱氨的酶促偶联。我们的数据揭示了一种通过超分子组装进行酶促偶联和抗噬菌体防御的有趣机制。