启动哺乳动物蛋白质合成和mRNA扫描机制
Ivan B Lomakin1, Thomas A Steitz
1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8114, USA. ivan.lomakin@yale.edu
Nature
|July 23, 2013
概括
研究人员可视化了真核细胞翻译启动的关键步骤,揭示了小核糖体子单元如何结合信使RNA (mRNA) 和扫描来启动蛋白质合成. 这些发现澄清了启动因子和mRNA扫描机制的作用.
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:
- 翻译启动对于真核细胞中的蛋白质合成至关重要.
- 小核糖体子单元扫描信使RNA (mRNA),以找到开始的编码子.
- 这个过程是由几个真核细胞启动因子 (eIF) 调节的.
研究的目的:
- 确定复合体的结构,这些复合体代表了哺乳动物翻译启动过程中的不同步骤.
- 阐明mRNA扫描和启动密码子识别背后的分子机制.
- 为了解真核细胞翻译启动过程中的动态相互作用提供见解.
主要方法:
- 电子显微镜 (Cryo-EM) 用于确定高分辨率结构.
- 核糖体复合体的生物化学分析.
- 对结合eIF1,eIF1A,mRNA和启动器tRNA的小核糖体亚单元复合物的结构分析.
主要成果:
- 在翻译启动过程中确定了小核糖体子单元的三个功能状态的详细结构.
- 揭示了关键启动因子 (eIF1,eIF1A),mRNA和启动tRNA在复合体内的确切位置.
- 与功能状态相关的形态变化提供了对核糖体动力学和mRNA-蛋白相互作用的见解.
结论:
- 这项研究为了解真核细胞翻译启动提供了结构基础.
- 这些发现揭示了mRNA扫描的机制,并启动了密码子选择.
- 结果为蛋白质合成启动的复杂过程提供了功能意义.
相关概念视频
Initiation of Translation
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...
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...
Initiation of Translation
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...
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...
Leaky Scanning
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...
Translation in Prokaryotes
Prokaryote translation is a complex, highly coordinated process that converts genetic information from mRNA into functional proteins. It involves three stages: initiation, elongation, and termination, each facilitated by specific molecular components.Initiation of TranslationThe process begins with the assembly of the ribosomal subunits and initiation factors on the mRNA. In bacteria, the 30S ribosomal subunit recognizes the Shine-Dalgarno sequence in the mRNA, a conserved region upstream of...
Ribosomal RNA Synthesis
Ribosome synthesis is a highly complex and coordinated process involving more than 200 assembly factors. The synthesis and processing of ribosomal components occurs not only in the nucleolus but also in the nucleoplasm and the cytoplasm of eukaryotic cells.
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
Ribosomal RNA Synthesis
Ribosome synthesis is a highly complex and coordinated process involving more than 200 assembly factors. The synthesis and processing of ribosomal components occurs not only in the nucleolus but also in the nucleoplasm and the cytoplasm of eukaryotic cells.
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...


