National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing, 100101, China.
School of Biological Sciences, University of Chinese Academy of Sciences, 19 Yuquan Road, Shijingshan District, Beijing, 100049, China.
Nat Commun. 2024 Jan 29;15(1):836. doi: 10.1038/s41467-024-45173-7.
The Gabija system is a newly discovered bacterial immune system that consists of GajA and GajB. Here we report the cryo-EM structure of the Gabija complex from Bacillus cereus VD045 at 3.6 Å, which provides the direct evidence of interactions between GajA and GajB. The Gabija complex is an octameric ring structure with four GajA and four GajB. GajA is an OLD nucleases family protein, while GajB belongs to the SF1 helicases. The Gabija complex has sequence-specific DNA nuclease activity and prefers circular rather than linear DNA as substrate, its activity is more sensitive to concentrations change of nucleotides compared to GajA alone. Our data suggest a mechanism of Gabija immunity: the nuclease activity of Gabija complex is inhibited under physiological conditions, while it is activated by depletion of NTP and dNTP upon the replication and transcription of invading phages and cleave the circular DNA to prevent phage DNA replication.
加比亚系统是一种新发现的细菌免疫系统,由 GajA 和 GajB 组成。在这里,我们报道了来自蜡状芽孢杆菌 VD045 的加比亚复合物的冷冻电镜结构,该结构提供了 GajA 和 GajB 之间相互作用的直接证据。加比亚复合物是一个具有四个 GajA 和四个 GajB 的八聚体环结构。GajA 是一个 OLD 核酸酶家族蛋白,而 GajB 属于 SF1 解旋酶。加比亚复合物具有序列特异性 DNA 核酸酶活性,更喜欢环状而不是线状 DNA 作为底物,与单独的 GajA 相比,其活性对核苷酸浓度变化更敏感。我们的数据表明了加比亚免疫的一种机制:在生理条件下,加比亚复合物的核酸酶活性受到抑制,而当入侵噬菌体的复制和转录导致 NTP 和 dNTP 耗尽时,它被激活,并切割环状 DNA 以防止噬菌体 DNA 复制。