Structural and functional insights into the roles of the Mms21 subunit of the Smc5/6 complex.

Structural and functional insights into the roles of the Mms21 subunit of the Smc5/6 complex.
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DOI:
10.1016/j.molcel.2009.06.032
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发表时间:
2009-09-11
期刊:
影响因子:
16
通讯作者:
Ye, Hong
Ye, Hong
中科院分区:
生物学1区
文献类型:
--
作者:
Duan, Xinyuan;Sarangi, Prabha;Liu, Xianpeng;Rangi, Gurdish K.;Zhao, Xiaolan;Ye, Hong

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Smc 5/6复合物是细胞生长和DNA修复所需的进化上保守的染色体ATP酶。它的Mms 21亚基通过与Smc 5的臂区对接并提供SUMO连接酶活性来支持这两种功能。在这里,我们报告的晶体结构的Mms 21在复杂的Smc 5 arm. Our结构揭示了两个不同的结构和功能域的Smc 5结合的Mms 21:其N-末端的一半是专门为Smc 5结合形成一个螺旋束与Smc 5的卷曲螺旋结构;其C-末端的一半包括SUMO连接酶域,它采用了一种新型的环E3结构。突变和结构分析表明,Mms 21-Smc 5界面是细胞生长和抵抗DNA损伤所必需的,而独特的Mms 21 RING结构域赋予SUMO E2-E3相互作用的特异性。通过基于结构的Mms 21功能的解剖,我们的研究建立了一个框架,了解其在Smc 5/6复合体中的作用。
The Smc5/6 complex is an evolutionarily conserved chromosomal ATPase required for cell growth and DNA repair. Its Mms21 subunit supports both functions by docking to the arm region of Smc5 and providing SUMO ligase activity. Here we report the crystal structure of Mms21 in complex with the Smc5 arm. Our structure revealed two distinct structural and functional domains of the Smc5-bound Mms21: its N-terminal half is dedicated to Smc5 binding by forming a helix bundle with a coiled-coil structure of Smc5; its C-terminal half includes the SUMO ligase domain, which adopts a new type of RING E3 structure. Mutagenesis and structural analyses showed that the Mms21-Smc5 interface is required for cell growth and resistance to DNA damage, while the unique Mms21 RING domain confers specificity to the SUMO E2–E3 interaction. Through structure-based dissection of Mms21 functions, our studies establish a framework for understanding its roles in the Smc5/6 complex.
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