近日，丹麦哥本哈根大学Nicholas M. I. Taylor等研究人员合作揭示了Zorya抗噬菌体防御系统的结构与机制。相关论文于2024年12月11日在线发表在《自然》杂志上。

通过冷冻电镜、突变分析、荧光显微镜、蛋白质组学和功能研究，研究人员探讨了Zorya防御的分子基础。研究人员展示了ZorAB的冷冻电镜结构，表明它与其他5:2内膜离子驱动旋转电动机共享化学计量比和特征。ZorA5B2复合物包含一个二聚体的ZorB胶质聚糖结合结构域和一个由ZorA构成的五聚体α-螺旋卷曲尾部，尾部大约延伸70纳米进入细胞质。

研究人员还表征了可溶性Zorya组分ZorC和ZorD的结构与功能，发现它们分别具有DNA结合和核酸酶活性。全面的功能和突变分析表明，所有Zorya组分协同工作，保护细菌细胞免受侵入的噬菌体。研究人员提供了证据表明，ZorAB作为一个质子驱动的电动机，在感知噬菌体入侵后被激活。随后，ZorAB通过ZorA细胞质尾部传递噬菌体入侵信号，招募并激活可溶性ZorC和ZorD效应分子，帮助降解噬菌体DNA。总之，该研究阐明了Zorya作为抗噬菌体防御系统的基本机制。

研究人员表示，Zorya是一种新近发现且广泛分布的细菌免疫系统，能够保护细菌免受病毒（噬菌体）感染。已发现三种Zorya亚型，每种亚型都包含预测的膜嵌入式ZorAB复合物，配有在Zorya亚型之间有所不同的可溶性亚基，特别是I型Zorya系统中的ZorC和ZorD。

附：英文原文

Title: Structure and mechanism of the Zorya anti-phage defense system

Author: Hu, Haidai, Popp, Philipp F., Hughes, Thomas C. D., Roa-Eguiara, Aritz, Rutbeek, Nicole R., Martin, Freddie J. O., Hendriks, Ivo Alexander, Payne, Leighton J., Yan, Yumeng, Humolli, Dorentina, Klein-Sousa, Victor, Songailiene, Inga, Wang, Yong, Nielsen, Michael Lund, Berry, Richard M., Harms, Alexander, Erhardt, Marc, Jackson, Simon A., Taylor, Nicholas M. I.

Issue&Volume: 2024-12-11

Abstract: Zorya is a recently identified and widely distributed bacterial immune system that protects bacteria from viral (phage) infections. Three Zorya subtypes have been discovered, each containing predicted membrane-embedded ZorAB complexes paired with soluble subunits that differ among Zorya subtypes, notably ZorC and ZorD in type I Zorya systems1,2. Here, we investigate the molecular basis of Zorya defense using cryo-electron microscopy, mutagenesis, fluorescence microscopy, proteomics, and functional studies. We present cryo-EM structures of ZorAB and show that it shares stoichiometry and features of other 5:2 inner membrane ion-driven rotary motors. The ZorA5B2 complex contains a dimeric ZorB peptidoglycan binding domain and a pentameric α-helical coiled-coil tail made of ZorA that projects approximately 70 nm into the cytoplasm. We also characterize the structure and function of the soluble Zorya components, ZorC and ZorD, finding that they harbour DNA binding and nuclease activity, respectively. Comprehensive functional and mutational analyses demonstrate that all Zorya components work in concert to protect bacterial cells against invading phages. We provide evidence that ZorAB operates as a proton-driven motor that becomes activated upon sensing of phage invasion. Subsequently, ZorAB transfers the phage invasion signal through the ZorA cytoplasmic tail to recruit and activate the soluble ZorC and ZorD effectors, which facilitate degradation of the phage DNA. In summary, our study elucidates the foundational mechanisms of Zorya function as an anti-phage defense system.

DOI: 10.1038/s41586-024-08493-8

Source: https://www.nature.com/articles/s41586-024-08493-8