Structural Analysis of Shu Proteins Reveals a DNA Binding Role Essential for Resisting Damage
Structural Analysis of Shu Proteins Reveals a DNA Binding Role Essential for Resisting Damage
复制标题
Shu 蛋白的结构分析揭示了抵抗损伤所必需的 DNA 结合作用
DOI：
10.1074/jbc.m111.334698
复制
发表时间：
2012-06-08
影响因子：
4.8
通讯作者：
Teng, Maikun
中科院分区：
文献类型：
--
作者：
Tao, Yuyong;Li, Xu;Teng, Maikun
酵母Shu复合体由蛋白Shu1、Shu2、Psy3和Csm2组成，通过将复制后修复与同源重组偶联来维持基因组的稳定性。然而，由于缺乏关于Shu蛋白的生化和结构信息，无法揭示它们在该通路中的确切作用。本文报道了Psy3-Csm2配合物的1.9埃晶体结构。晶体结构表明，Psy3主要通过疏水核与Csm2形成异源二聚体。出乎意料的是，Psy3和Csm2共享一个与Rad51的ATPase核心域非常相似的架构。在Psy3和Csm2中存在的L2环与Rad51相似，并赋予Shu复合物的DNA结合活性。与Rad51一样，Shu复合体似乎通过非特异性结合DNA而形成核蛋白丝。基于结构的诱变研究表明，Shu复合物的DNA结合活性对于甲基磺酸盐诱导的DNA损伤的修复至关重要。我们的发现为了解Shu复合体对Srs2的调控提供了良好的基础。
The yeast Shu complex, consisting of the proteins Shu1, Shu2, Psy3, and Csm2, maintains genomic stability by coupling post-replication repair to homologous recombination. However, a lack of biochemical and structural information on the Shu proteins precludes revealing their precise roles within the pathway. Here, we report on the 1.9-angstrom crystal structure of the Psy3-Csm2 complex. The crystal structure shows that Psy3 forms a heterodimer with Csm2 mainly through a hydrophobic core. Unexpectedly, Psy3 and Csm2 share a similar architecture that closely resembles the ATPase core domain of Rad51. The L2 loop present in Psy3 and Csm2 is similar to that of Rad51 and confers the DNA binding activity of the Shu complex. As with Rad51, the Shu complex appears to form a nucleoprotein filament by binding nonspecifically to DNA. Structure-based mutagenesis studies have demonstrated that the DNA binding activity of the Shu complex is essential for repair of the methyl methanesulfonate-induced DNA damage. Our findings provide good foundations for the understanding of the Srs2 regulation by the Shu complex.