Duan Xinyuan, Sarangi Prabha, Liu Xianpeng, Rangi Gurdish K, Zhao Xiaolan, Ye Hong
James Graham Brown Cancer Center, University of Louisville, KY 40202, USA.
Mol Cell. 2009 Sep 11;35(5):657-68. doi: 10.1016/j.molcel.2009.06.032.
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.
Smc5/6复合物是一种在进化上保守的染色体ATP酶，是细胞生长和DNA修复所必需的。其Mms21亚基通过与Smc5的臂区域对接并提供SUMO连接酶活性来支持这两种功能。在此，我们报道了与Smc5臂结合的Mms21的晶体结构。我们的结构揭示了与Smc5结合的Mms21的两个不同的结构和功能结构域：其N端一半通过与Smc5的卷曲螺旋结构形成螺旋束而专门用于Smc5结合；其C端一半包括SUMO连接酶结构域，该结构域采用一种新型的RING E3结构。诱变和结构分析表明，Mms21-Smc5界面是细胞生长和对DNA损伤抗性所必需的，而独特的Mms21 RING结构域赋予SUMO E2-E3相互作用特异性。通过基于结构的Mms21功能剖析，我们的研究建立了一个理解其在Smc5/6复合物中作用的框架。
