REDOX-DEPENDENT SHIFT OF OXYR-DNA CONTACTS ALONG AN EXTENDED DNA-BINDING SITE - A MECHANISM FOR DIFFERENTIAL PROMOTER SELECTION
REDOX-DEPENDENT SHIFT OF OXYR-DNA CONTACTS ALONG AN EXTENDED DNA-BINDING SITE - A MECHANISM FOR DIFFERENTIAL PROMOTER SELECTION
复制标题
DOI：
10.1016/s0092-8674(94)90702-1
复制
发表时间：
1994-09-09
期刊：
影响因子：
64.5
通讯作者：
STORZ, G
中科院分区：
文献类型：
--
作者：
TOLEDANO, MB;KULLIK, I;STORZ, G
氧化还原敏感的 OxyR 蛋白会激活抗氧化防御基因的转录以响应氧化应激，并在氧化和还原条件下抑制其自身表达。先前的研究表明，OxyR 结合位点异常长，且序列相似性有限。在这里，我们报告氧化的 OxyR 识别由四个以 10 bp 间隔间隔的 ATAGnt 元件组成的基序，并在 DNA 螺旋一个面上的四个相邻主沟中接触这些元件。相反，还原的OxyR接触由一圈螺旋分隔开的两对相邻的主凹槽。这两种结合模式对于 OxyR 在体内发挥激活剂和阻抑剂的作用至关重要。我们提出，OxyR 四聚体的特异性 DNA 识别是通过四个中等亲和力的接触来实现的，允许 OxyR 在细胞氧化还原状态改变时重新定位其 DNA 接触并靶向替代的启动子组。
The redox-sensitive OxyR protein activates the transcription of antioxidant defense genes in response to oxidative stress and represses its own expression under both oxidizing and reducing conditions. Previous studies showed that OxyR-binding sites are unusually long with limited sequence similarity. Here, we report that oxidized OxyR recognizes a motif comprised of four ATAGnt elements spaced at 10 bp intervals and contacts these elements in four adjacent major grooves on one face of the DNA helix. In contrast, reduced OxyR contacts two pairs of adjacent major grooves separated by one helical turn. The two modes of binding are essential for OxyR to function as both an activator and a repressor in vivo. We propose that specific DNA recognition by an OxyR tetramer is achieved with four contacts of intermediate affinity allowing OxyR to reposition its DNA contacts and target alternate sets of promoters as the cellular redox state is altered.