Structural basis for broad anti-phage immunity by DISARM.
Structural basis for broad anti-phage immunity by DISARM.
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DOI：
10.1038/s41467-022-30673-1
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发表时间：
2022-05-27
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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作者：
在与噬菌体的进化军备竞赛中，细菌已经组装了各种各样的抗病毒免疫策略。虽然最近发现的Disarm(与限制修饰相关的防御岛系统)系统可以提供对多种噬菌体的保护，但支持广泛的抗病毒靶向但避免自身免疫的分子机制仍然是个谜。在这里，我们报告了核心解除武装复合体DrmAB的冷冻EM结构，无论是单独的还是与未甲基化的噬菌体DNA模拟物形成的复合体。这些结构揭示了DrmAB核心复合体被DrmA内的触发环(TL)自动抑制，并与含有5‘悬垂的DNA底物结合移位TL，启动了DrmAB激活的远程结构重排。结合体内结构指导的研究，我们的工作为噬菌体DNA识别和这一广泛存在的抗病毒防御系统的特异性激活的机制提供了见解。Disarm(与限制修改相关的防御岛系统)系统可以为细菌提供针对广泛噬菌体的保护。这里，Bravo等人。确定核心解除武装复合体的冷冻-EM结构，揭示噬菌体DNA识别和激活这一广泛的防御系统。
In the evolutionary arms race against phage, bacteria have assembled a diverse arsenal of antiviral immune strategies. While the recently discovered DISARM (Defense Island System Associated with Restriction-Modification) systems can provide protection against a wide range of phage, the molecular mechanisms that underpin broad antiviral targeting but avoiding autoimmunity remain enigmatic. Here, we report cryo-EM structures of the core DISARM complex, DrmAB, both alone and in complex with an unmethylated phage DNA mimetic. These structures reveal that DrmAB core complex is autoinhibited by a trigger loop (TL) within DrmA and binding to DNA substrates containing a 5′ overhang dislodges the TL, initiating a long-range structural rearrangement for DrmAB activation. Together with structure-guided in vivo studies, our work provides insights into the mechanism of phage DNA recognition and specific activation of this widespread antiviral defense system. DISARM (Defense Island System Associated with Restriction Modification) systems can provide bacteria with protection against a wide range of phage. Here, Bravo et al. determine cryo-EM structures of the core DISARM complex that shed light onto phage DNA recognition and activation of this widespread defense system.
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影响因子：
64.8
作者：
Levy A;Goren MG;Yosef I;Auster O;Manor M;Amitai G;Edgar R;Qimron U;Sorek R
通讯作者：
Sorek R
DOI：
10.1073/pnas.1913546116
发表时间：
2019-12-03
影响因子：
11.1
作者：
Jia, Ning;Unciuleac, Mihaela C.;Shuman, Stewart
通讯作者：
Shuman, Stewart
DOI：
10.1107/s2059798318006551
发表时间：
2018-06-01
期刊：
Acta crystallographica. Section D, Structural biology
影响因子：
--
作者：
Afonine PV;Poon BK;Read RJ;Sobolev OV;Terwilliger TC;Urzhumtsev A;Adams PD
通讯作者：
Adams PD
影响因子：
30.3
作者：
Fang FC;Frawley ER;Tapscott T;Vázquez-Torres A
通讯作者：
Vázquez-Torres A
DOI：
10.1126/science.aar4120
发表时间：
2018-03-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Doron S;Melamed S;Ofir G;Leavitt A;Lopatina A;Keren M;Amitai G;Sorek R
通讯作者：
Sorek R