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Structural insights into assembly, operation and inhibition of a type I restriction-modification system.
Nature Microbiology ( IF 28.3 ) Pub Date : 2020-06-01 , DOI: 10.1038/s41564-020-0731-z
Yina Gao 1 , Duanfang Cao 2 , Jingpeng Zhu 1, 3 , Han Feng 1 , Xiu Luo 1, 3 , Songqing Liu 1 , Xiao-Xue Yan 2 , Xinzheng Zhang 2 , Pu Gao 1
Affiliation  

Type I restriction–modification (R–M) systems are widespread in prokaryotic genomes and provide robust protection against foreign DNA. They are multisubunit enzymes with methyltransferase, endonuclease and translocase activities. Despite extensive studies over the past five decades, little is known about the molecular mechanisms of these sophisticated machines. Here, we report the cryo-electron microscopy structures of the representative EcoR124I R–M system in different assemblies (R2M2S1, R1M2S1 and M2S1) bound to target DNA and the phage and mobile genetic element-encoded anti-restriction proteins Ocr and ArdA. EcoR124I can precisely regulate different enzymatic activities by adopting distinct conformations. The marked conformational transitions of EcoR124I are dependent on the intrinsic flexibility at both the individual-subunit and assembled-complex levels. Moreover, Ocr and ArdA use a DNA-mimicry strategy to inhibit multiple activities, but do not block the conformational transitions of the complexes. These structural findings, complemented by mutational studies of key intermolecular contacts, provide insights into assembly, operation and inhibition mechanisms of type I R–M systems.



中文翻译:

对I型限制性修饰系统的组装,操作和抑制的结构见解。

I型限制性修饰(R–M)系统广泛存在于原核生物基因组中,并提供了针对外来DNA的强大保护。它们是具有甲基转移酶,核酸内切酶和转位酶活性的多亚基酶。尽管在过去的五十年中进行了广泛的研究,但对这些复杂机器的分子机理知之甚少。在这里,我们报告了具有代表性的EcoR124I R–M系统在不同组件(R 2 M 2 S 1,R 1 M 2 S 1和M 2 S 1)结合到目标DNA和噬菌体以及流动遗传元件编码的抗限制性蛋白Ocr和ArdA。EcoR124I通过采用不同的构象可以精确调节不同的酶活性。EcoR124I的显着构象转变取决于单个亚基和组装复合物水平的固有柔性。此外,Ocr和ArdA使用DNA模仿策略来抑制多种活性,但不阻止复合物的构象转变。这些结构上的发现,以及对关键分子间接触的突变研究的补充,提供了对IR–M型系统的组装,操作和抑制机制的见解。

更新日期:2020-06-01
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