转录因子NF-kappaB与DNA结合的p50/p65异构体的晶体结构
F E Chen1, D B Huang, Y Q Chen
1Department of Biology, University of California, San Diego, La Jolla 92093-0359, USA.
Nature
|February 5, 1998
概括
与DNA结合的NF-kappaB p50/p65异构体的晶体结构揭示了每个子单元的特定结合点. 这一发现解释了异构体强的接口和可变的DNA序列依赖性构造.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 遗传学 是一个遗传学.
背景情况:
- 核因子kappa B (NF-kappaB) 转录因子调节关键的细胞过程,包括免疫反应和发育.
- NF-kappaB p50/p65异构体,一个关键的Rel家族成员,与kappaB DNA元素结合,控制基因表达.
- 抑制剂kappaB蛋白通过信号诱导机制调节NF-kappaB的局部化和活性.
研究的目的:
- 确定与kappaB DNA结合的NF-kappaB p50/p65异构体的晶体结构.
- 阐明异构体的DNA结合特异性和接口强度的结构基础.
- 了解DNA序列如何影响rel家族二元体的构造.
主要方法:
- 在2.9A分辨率的X射线晶体学.
- 与免疫球蛋白轻链基因的kappaB DNA增强剂共同结晶的p50/p65异构体.
- 与其他Rel家族二度体进行结构比较分析.
主要成果:
- 晶体结构揭示了不同的DNA结合子位点:p50的5'基对5'子位点和p65的4'基对3'子位点.
- 该结构解释了p50/p65异构体与同构体相比的增强结合接口.
- 观察到Rel二次元子单元的形状变异性,这取决于DNA序列.
结论:
- 确定的结构为NF-kappaB p50/p65DNA识别和结合提供了原子层面的洞察力.
- 这些发现澄清了NF-kappaB异构体与各种促进物的差异性行为背后的分子机制.
- 这些结构信息对于理解NF-kappaB介导的基因调节在不同细胞环境中至关重要.
相关概念视频
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