干扰素β增强体的原子模型
Daniel Panne1, Tom Maniatis, Stephen C Harrison
1The Jack and Eileen Connors Structural Biology Laboratory, Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology, Howard Hughes Medical Institute, 250 Longwood Avenue, Boston, MA 02115, USA.
Cell
|June 19, 2007
概括
干扰素β (IFNβ) 基因是干扰素β (IFNβ) 的基因.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 免疫学 免疫学 免疫学
背景情况:
- 干扰素-β (IFN-β) 基因的转录激活取决于一种称为增强酶体的蛋白质复合物的组装.
- 增强酶体包括转录因子ATF-2/c-Jun,干扰素调节因子3 (IRF-3) /IRF-7,以及激活B细胞的核因子kappa-光链增强剂 (NFkappaB).
- 这些因素以合作方式与IFN-β增强剂结合,将联合激活剂和染色体重塑蛋白与促进剂招募在一起.
研究的目的:
- 阐明增强酶体组合和DNA结合的结构基础.
- 了解转录因子的合作结合是如何实现的.
- 解释IFN-β增强剂序列的进化保存.
主要方法:
- 确定了IRF-3,IRF-7和NFkappaB与IFN-β增强剂的一半结合的DNA结合域的晶体结构.
- 将这个结构与之前解决的增强器另一半的结构集成.
- 在IFN-β增强器组装了增强酶结构的完整模型.
主要成果:
- 八种蛋白质的结合形成了一个连续的表面,用于结合IFN-β增强剂的复合DNA元素.
- 增强酶体内的有限的直接蛋白质-蛋白质接触表明DNA形状的变化和与协同激活剂 (例如CBP) 的相互作用介导合作结合.
- 蛋白质复合体和几乎所有DNA核酸对之间的广泛接触解释了增强剂的序列不变性.
结论:
- 该研究提供了IFN-β增强体的详细结构模型.
- 合作结合是通过DNA曲和与协活性剂的相互作用来促进的,而不是广泛的蛋白质-蛋白质接口.
- 与DNA的全面相互作用强调了IFN-β增强剂的功能重要性和进化保护.
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