人类eIF4A/4G/4H直酶复合体在翻译启动中的拓和调节
Assen Marintchev1, Katherine A Edmonds, Boriana Marintcheva
1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA. amarint@bu.edu
Cell
|February 11, 2009
概括
细胞启动因子4A (eIF4A) 酶复合结构揭示了辅助蛋白质eIF4G和eIF4H如何刺激其mRNA解活动. 这些蛋白调节eIF4AA.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 在转化启动过程中,mRNA解和扫描过程中,RNA螺旋酶真核细胞启动因子4A (eIF4A) 是至关重要的.
- 自由eIF4A表现出有限的螺旋酶活性,需要与辅助蛋白如eIF4G和eIF4H相互作用以进行功能刺激.
- 精确的结构组织和eIF4A酶复合物的机械细节在很大程度上仍未确定.
研究的目的:
- 阐明eIF4A/4G/4H螺旋酶复合体内的三维拓和域-域相互作用.
- 研究ATP结合和水解周期期间相互作用的动态重排.
- 了解辅助蛋白质eIF4G和eIF4H如何调节eIF4A对ATP的亲和力及其整体酶活性.
主要方法:
- 利用对域-域接触的实验观测来确定该复合体的拓.
- 分析了ATP结合/水解周期,以观察动态相互作用的重新安排.
- 研究了辅助蛋白与eIF4A双酶域的同时相互作用.
主要成果:
- 该研究确定了eIF4A/4G/4H螺旋酶复合物的拓,其特点是经过实验观察到的多个域-域接触.
- 证明了复合体内的特定相互作用在整个ATP结合和水解周期中经历了持续的重组.
- 表明eIF4G和eIF4H通过与两个酶域相互作用来调节eIF4A的ATP亲和力,稳定闭合 (ATP结合) 或开放 (无核酸) 构造.
结论:
- 确定的复杂拓和动态相互作用为eIF4A直酶活性的刺激提供了机理性的洞察力.
- RNA结合表面的空间布局是了解mRNA解和扫描作用的关键.
- 辅助蛋白质通过形状调制和相互作用动态来调节eIF4A功能,起着至关重要的作用.
相关概念视频
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02:35Transcription Elongation Factors
Transcription elongation is a dynamic process that alters depending upon the sequence heterogeneity of the DNA being transcribed. Hence, it is not surprising that the elongation complex's composition also varies along the way while transcribing a gene.
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA into a...
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Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
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