Structure and DNA damage-dependent derepression mechanism for the XRE family member DG-DdrO
Structure and DNA damage-dependent derepression mechanism for the XRE family member DG-DdrO
复制标题
XRE家族成员DG-DdrO的结构和DNA损伤依赖性去抑制机制
DOI：
10.1093/nar/gkz720
复制
发表时间：
2019-10-10
影响因子：
14.9
通讯作者：
Hua, Yuejin
中科院分区：
文献类型：
--
作者：
Lu, Huizhi;Wang, Liangyan;Hua, Yuejin
DdrO是XRE家族的转录抑制因子，与金属蛋白酶PprI协同作用，在异常球菌属物种的DNA损伤反应中至关重要。本文报道了地热奇球菌DdrO的晶体结构。生物化学和结构研究揭示了DdrO蛋白的保守识别α-螺旋和扩展的二聚体相互作用，这是启动子DNA结合所必需的。XRE家族蛋白的HTH基序中的两个保守的带相反电荷的残基形成盐桥相互作用，这对于启动子DNA结合是必需的。值得注意的是，C-末端结构域通过富含亮氨酸/异亮氨酸的螺旋的疏水相互作用来稳定，这对于DdrO二聚化是至关重要的。我们的研究结果表明，DdrO是一种新的XRE家族转录调节因子，形成一个独特的二聚体。该结构也提供了深入了解DdrO-PprI介导的异常球菌DNA损伤反应的机制。
DdrO is an XRE family transcription repressor that, in coordination with the metalloprotease PprI, is critical in the DNA damage response of Deinococcus species. Here, we report the crystal structure of Deinococcus geothermalis DdrO. Biochemical and structural studies revealed the conserved recognizing alpha-helix and extended dimeric interaction of the DdrO protein, which are essential for promoter DNA binding. Two conserved oppositely charged residues in the HTH motif of XRE family proteins form salt bridge interactions that are essential for promoter DNA binding. Notably, the C-terminal domain is stabilized by hydrophobic interactions of leucine/isoleucine-rich helices, which is critical for DdrO dimerization. Our findings suggest that DdrO is a novel XRE family transcriptional regulator that forms a distinctive dimer. The structure also provides insight into the mechanism of DdrO-PprI-mediated DNA damage response in Deinococcus.