近日，武汉大学王隆飞等研究人员合作揭示Gabija抗噬菌体系统的结构和激活机制。2024年3月12日，《自然》杂志在线发表了这项成果。

研究人员表示，原核生物已经演化出复杂的先天免疫系统来抵御噬菌体感染。Gabija是一种高度丰富的原核生物防御系统，由GajA和GajB两种成分组成。研究人员以前曾证实，GajA的功能是一种DNA内切酶，在ATP存在时不活跃。

为了揭示Gabija系统是如何在抗噬菌体防御中被激活的，研究人员报告了它在五种状态下的冷冻电镜（cryo-EM）结构，包括apo GajA、与DNA复合的GajA、与ATP结合的GajA、apo GajA-GajB以及与ATP/Mg²⁺复合的GajA-GajB。GajA是一个菱形四聚体，其ATP酶结构域位于中心，Toprim结构域位于外围。ATP酶结构域上的ATP结合可稳定ATP酶结构域内的插入区域，使Toprim结构域处于封闭状态。当噬菌体耗尽ATP时，Toprim结构域打开，与DNA底物结合并切割DNA底物。停靠在GajA上的GajB被切割的DNA激活，最终导致原核细胞死亡。这项研究展示了Gajiba激活的机理。

附：英文原文

Title: Structures and activation mechanism of the Gabija anti-phage system

Author: Li, Jing, Cheng, Rui, Wang, Zhiming, Yuan, Wuliu, Xiao, Jun, Zhao, Xinyuan, Du, Xinran, Xia, Shiyu, Wang, Lianrong, Zhu, Bin, Wang, Longfei

Issue&Volume: 2024-03-12

Abstract: Prokaryotes have evolved intricate innate immune systems against phage infection1-7. Gabija is a highly abundant prokaryotic defense system consisting of two components, GajA and GajB8. We previously demonstrated that GajA functions as a DNA endonuclease that is inactive in the presence of ATP9. To reveal how the Gabija system is activated for anti-phage defense, we report its cryo-electron microscopy (cryo-EM) structures in five states, including apo GajA, GajA in complex with DNA, GajA bound by ATP, apo GajA-GajB, and GajA-GajB in complex with ATP/Mg2+. GajA is a rhombus-shaped tetramer with its ATPase domain clustered at the center and the Toprim domain located peripherally. ATP binding at the ATPase domain stabilizes the insertion region within the ATPase domain, keeping the Toprim domain in a closed state. Upon ATP depletion by phages, the Toprim domain opens to bind and cleave the DNA substrate. GajB, which docks on GajA, is activated by the cleaved DNA, ultimately leading to prokaryotic cell death. Our study presents a mechanistic landscape of Gajiba activation.

DOI: 10.1038/s41586-024-07270-x

Source: https://www.nature.com/articles/s41586-024-07270-x