在bcl-2 P1促销器中的i-motif形成了一个意想不到的稳定结构,具有独特的8:5:7循环折叠模式
Samantha Kendrick1, Yoshitsugu Akiyama, Sidney M Hecht
1Arizona Cancer Center, 1515 North Campbell Avenue, Tucson, Arizona 85724, USA.
Journal of the American Chemical Society
|November 14, 2009
概括
在BCL-2促销器.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物化学 生物化学
背景情况:
- bcl-2原型瘤基因的转录调节是复杂的,涉及P1促进蛋白和调节蛋白.
- 在P1位点上游的富含GC的区域对于bcl-2促进体活性至关重要.
- 这种富含GC的区域可以形成G-quadruplex和i-motif DNA的二次结构.
研究的目的:
- 通过bcl-2促进体的富含聚胺氨酸的链来研究i-动机DNA二次结构的形成.
- 为了描述bcl-2i-motif结构的折叠模式和稳定性.
- 探索这种结构对蛋白质和小分子识别的潜力.
主要方法:
- 突变研究研究 突变研究
- 循环二合色 (CD) 光谱法 循环二合色 (CD) 光谱法
- 热稳定性分析分析热稳定性分析
- 化学足迹 () 是一种化学足迹.
- 光胺模拟合并测试光胺模拟合并测试.
主要成果:
- 富含多聚胺的链形成了一个主要的分子内i-motif结构,过渡pH值为6.6.
- 在pH值6.1下, 8:5:7循环构造是主要的结构,通过多种方法得到证实.
- 观察到证据表明,在顶环区域有一个封闭结构.
- 该i-motif结构呈现了蛋白质和小分子相互作用的潜在地点.
结论:
- bcl-2促进体的富含GC的区域可以形成i-motif DNA的二次结构.
- 对非B-DNA的合规转换可能会调节bcl-2转录.
- i-motif结构为治疗向提供了新的可能性.
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