作为Vmw65 (VP16) 差异识别的基础的Oct-1 POU域-DNA复合物的特定位点的形状变化
Cell
|December 2, 1994
概括
围绕POU域的调节元件通过诱导特定的DNA结合形态来决定Vmw65 (VP16) 相互作用. 突变显示这种形状变化对于Vmw65识别至关重要,而不仅仅是POU结合.
科学领域:
- 分子生物学分子生物学
- 蛋白质-DNA相互作用
- 转录条例 转录条例 转录条例
背景情况:
- 该POU域是一个DNA结合动机,对于转录调节至关重要.
- Vmw65 (VP16) 是一种与POU域蛋白相互作用的病毒交互激活器.
- 围绕DNA结合部位的调节元素可以影响蛋白质-DNA复合体的形成和功能.
研究的目的:
- 为了研究在POU域-DNA复合体形成和Vmw65 (VP16) 相互作用中,围绕八合体位点的cis作用元素的作用.
- 为了确定这个侧面元素是否会在DNA结合时诱导POU域的构造变化.
- 阐明Vmw65 (VP16) 选择性在POU域识别中的结构基础.
主要方法:
- 局部导向的Cis作用调节元件和POU域的家庭主体的突变发生.
- 对POU域与DNA动机结合的分析.
- 评估Vmw65 (VP16) 与修饰POU-DNA复合物的相互作用.
主要成果:
- 侧面的cis-acting元素虽然对POU结合不至关重要,但会诱导POU域-DNA复合体的形状变化.
- 侧面元件的单次替换会扭曲POU复合体,防止Vmw65 (VP16) 相互作用而不影响POU结合.
- 在GARAT区域接触所涉及的家庭主域残留物的替换改变了DNA结合模式,并降低了Vmw65 (VP16) 的识别.
结论:
- Vmw65 (VP16) 识别了POU域的特定构造,这种构造是由侧面GARAT区域的存在引起的.
- 附带的调节元件在调节POU域功能和Vmw65 (VP16) 交易激活方面发挥着至关重要的作用.
- POU域的结构可塑性是转录调节中选择性蛋白质-蛋白质相互作用的关键.
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Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
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