Crystal structure of the human MUS81-EME2 complex
Crystal structure of the human MUS81-EME2 complex
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DOI：
10.1016/j.str.2022.02.015
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发表时间：
2022-05-05
期刊：
影响因子：
5.7
通讯作者：
Lin, Zhonghui
中科院分区：
文献类型：
--
作者：
Hua, Zhengkang;Fang, Qianqian;Lin, Zhonghui
MUS 81是一种重要的结构特异性核酸内切酶，负责加工停滞的复制叉和重组中间体。在人类中，MUS 81通过与其调节亚基EME 1和EME 2形成复合物来发挥功能，在G2/M和S期发挥不同的作用。虽然MUS 81-EME 1的结构已被深入研究，但没有关于MUS 81-EME 2的结构信息。在这里，我们报告了MUS 81-EME 2的晶体结构，其揭示了与MUS 81-EME 1复合物相似的整体蛋白质折叠。进一步的生化和结构表征表明，MUS 81-EME 1和MUS 81-EME 2复合物在体外底物识别和核酸内切酶活性方面是相同的，这意味着这两种复合物的不同细胞作用可能来自细胞中的时间控制。最后，一个广泛的结构指导的诱变分析提供了MUS 81-EME内切核酸酶如何识别各种DNA底物的结构选择性方式的分子基础的影响。
MUS81 is an important structure-specific endonuclease responsible for the processing of stalled replication forks and recombination intermediates. In human, MUS81 functions by forming complexes with its regulatory subunits EME1 and EME2, playing distinct roles in G2/M and S phases. Although the structures of MUS81-EME1 have been intensively studied, there is no structure information available about MUS81-EME2. Here, we report the crystal structure of MUS81-EME2, which reveals an overall protein fold similar to that of MUS81-EME1 complex. Further biochemical and structural characterization shows that the MUS81-EME1 and MUS81-EME2 complexes are identical in substrate recognition and endonuclease activities in vitro, implying that the distinct cellular roles of the two complexes could arise from temporal controls in cells. Finally, an extensive structure-guided mutagenesis analysis provides implications for the molecular basis of how the MUS81-EME endonucleases recognize various DNA substrates in a structure-selective manner.