一种对核糖体解码原理的新理解
Natalia Demeshkina1, Lasse Jenner, Eric Westhof
1Département de Biologie et de Génomique Structurales, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch 67400, France.
Nature
|March 23, 2012
概括
核糖体通过校对转移RNA (tRNA) 和信使RNA (mRNA) 相互作用来确保精确的蛋白质合成. 结构分析揭示了核糖体是如何形成的.
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:
- 在蛋白质合成过程中,核糖体选择基于信使RNA (mRNA) 编码的转移RNA (tRNA).
- 延长因子Tu (EF-Tu) 提供tRNA,GTP水解由子-子相互作用触发.
- 接下来是一个校对步骤,其中核糖体拒绝不匹配的tRNAs.
研究的目的:
- 阐明tRNA选择和校对在核糖体的解码中心的综合机制.
- 调查30S子单元在解码精度上的构造变化的作用.
主要方法:
- 在3.1-3.4 Å分辨率下确定了70S核糖体的六个X射线结构.
- 在校对步骤期间,在解码中心内建模的同源和近同源tRNA状态.
主要成果:
- 30S核糖体子单元在同源和近同源tRNA结合时经历相同的域关闭.
- 这种形状变化约束了mRNA,有利于沃森-克里克基配对在前两个码头-反码头位置.
- 解码中心迫使摇摆的基对 (U·G,G·U) 进入正规的C·G几何形状,导致近同源tRNA解离.
结论:
- 核糖体采用一种构造机制,在tRNA选择过程中强制执行忠实性.
- 解码中心积极纠正或拒绝非正规的基对,确保精确的蛋白质合成.
相关概念视频
The Central Dogma
Overview
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...
Termination of Translation
The large ribosomal subunit has several important structures essential to translation. These include the peptidyl transferase center (PTC) - which is the site where the peptide bond is formed - and a large, internal, water-filled tube through which the nascent polypeptide moves. This latter structure is called the Peptide Exit Tunnel, and it begins at the PTC and spans the body of the large ribosomal subunit. During translation, as the nascent polypeptide chain is synthesized, it passes through...
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...
Ribosome Profiling
Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique helps...
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique helps...
The Central Dogma
The central dogma explains the flow of genetic information from DNA nucleotides to the amino acid sequence of proteins.
RNA is the Missing Link Between DNA and Proteins
In the early 1900s, scientists discovered that DNA stores all the information needed for cellular functions and that proteins perform most of these functions. However, the mechanisms of converting genetic information into functional proteins remained unknown for many years. Initially, it was believed that a single gene is...
RNA is the Missing Link Between DNA and Proteins
In the early 1900s, scientists discovered that DNA stores all the information needed for cellular functions and that proteins perform most of these functions. However, the mechanisms of converting genetic information into functional proteins remained unknown for many years. Initially, it was believed that a single gene is...


