艾滋病毒-1 RRE干循环II的结构确定了高亲和度Rev结合点的两个构造状态
Jerricho Tipo1,2, Keerthi Gottipati2, Michael Slaton2
1Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX, 77555, USA.
Nature communications
|May 17, 2024
概括
艾滋病毒Rev蛋白与Rev响应元素 (RRE) 的相互作用对于病毒RNA输出至关重要. 结构分析揭示了RRE干循环II.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 病毒学 病毒学
背景情况:
- 艾滋病毒-1感染需要核出口未连接的病毒RNA.
- Rev反应元件 (RRE) 和Rev蛋白调解了这一重要的出口途径.
- 了解RRE-Rev相互作用是针对HIV复制的关键.
研究的目的:
- 阐明Rev蛋白与RRE干循环II结合的结构基础.
- 描述RRE干循环II的结构动态.
- 提出一个连续Rev与RRE结合的模型.
主要方法:
- 进行X射线晶体学以确定RRE茎循环II结构.
- Rev结合试验用于量化蛋白质-RNA相互作用.
- 不同的RRE形状的结构分析.
主要成果:
- 晶体结构揭示了RRE干循环II在封闭和开放的构造.
- 高亲和度Rev结合部位位于三向结合处,而不是干IIB.
- 截然不同的非规范性相互作用定义了封闭和开放的适配体,开放的形式促进了Rev结合.
结论:
- 开放的RRE干环II形状呈现了一个扩大的主要槽,用于初始的Rev蛋白相互作用.
- RRE干环II具有Rev二次体的高亲和和低亲和结合点.
- 提出了一种通过Rev诱导的结构重排的顺序结合部位形成模型.
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