Nicking mechanism underlying the DNA phosphorothioate-sensing antiphage defense by SspE.
Nicking mechanism underlying the DNA phosphorothioate-sensing antiphage defense by SspE.
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SspE 的 DNA 硫代磷酸酯感应抗噬菌体防御的切口机制。
DOI：
10.1038/s41467-022-34505-0
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发表时间：
2022-11-09
影响因子：
16.6
通讯作者：
Wang, Lianrong
中科院分区：
文献类型：
--
作者：
Gao, Haiyan;Gong, Xinqi;Zhou, Jinchuan;Zhang, Yubing;Duan, Jinsong;Wei, Yue;Chen, Liuqing;Deng, Zixin;Wang, Jiawei;Chen, Shi;Wu, Geng;Wang, Lianrong
DNA硫代磷酸酯（PT）修饰，用硫取代非桥磷酸氧，代表了原核生物中广泛的表观遗传标记，并提供对遗传寄生虫的保护。在基于PT的防御系统Ssp中，SspABCD赋予宿主DNA 5 '-CPSCA-3'基序中的单链PT修饰，SspE阻碍噬菌体繁殖。SspE依赖于宿主DNA中的PT修饰来发挥抗噬菌体活性。在这里，结构和生化分析表明，SspE优先招募PT网站介导的联合行动，其N-末端结构域（NTD）的疏水腔和C-末端结构域（CTD）的DNA结合区。PT识别扩大了GTP结合口袋，从而增加GTP水解活性，随后触发SspE从闭合状态到开放状态的构象转换。闭合到开放的转变促进SspE从自身PT-DNA解离并开启CTD的DNA切口核酸酶活性，使得SspE能够实现自我-非自我辨别并限制噬菌体捕食，即使在细菌基因组中只有一小部分可修饰的共有序列是PT保护的。SspABCD-SspE是一种硫代磷酸敏感的细菌防御系统。在这里，作者发现SspE利用DNA硫代磷酸化结合偏好来调节其自身/非自身辨别和噬菌体抗性的生化活性。
DNA phosphorothioate (PT) modification, with a nonbridging phosphate oxygen substituted by sulfur, represents a widespread epigenetic marker in prokaryotes and provides protection against genetic parasites. In the PT-based defense system Ssp, SspABCD confers a single-stranded PT modification of host DNA in the 5′-CPSCA-3′ motif and SspE impedes phage propagation. SspE relies on PT modification in host DNA to exert antiphage activity. Here, structural and biochemical analyses reveal that SspE is preferentially recruited to PT sites mediated by the joint action of its N-terminal domain (NTD) hydrophobic cavity and C-terminal domain (CTD) DNA binding region. PT recognition enlarges the GTP-binding pocket, thereby increasing GTP hydrolysis activity, which subsequently triggers a conformational switch of SspE from a closed to an open state. The closed-to-open transition promotes the dissociation of SspE from self PT-DNA and turns on the DNA nicking nuclease activity of CTD, enabling SspE to accomplish self-nonself discrimination and limit phage predation, even when only a small fraction of modifiable consensus sequences is PT-protected in a bacterial genome. SspABCD–SspE is a phosphorothioation-sensing bacterial defence system. Here, authors find that SspE exploits DNA phosphorothioation-binding preference to modulate its biochemical activities for the self/nonself discrimination and phage resistance.
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影响因子：
5.8
作者：
Pronk, Sander;Pall, Szilard;Lindahl, Erik
通讯作者：
Lindahl, Erik
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
dnd 基因对细菌中 DNA 进行硫代磷酸化
影响因子：
14.8
作者：
Wang, Lianrong;Chen, Shi;Dedon, Peter C.
通讯作者：
Dedon, Peter C.
影响因子：
2.9
作者：
Eastberg, Jennifer H.;Eklund, Jennifer;Stoddard, Barry L.
通讯作者：
Stoddard, Barry L.
影响因子：
14.9
作者：
Mierzejewska, Karolina;Bochtler, Matthias;Czapinska, Honorata
通讯作者：
Czapinska, Honorata