相关实验视频
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Xenopus laevis as a Model to Identify Translation Impairment
Published on: September 27, 2015
普遍翻译启动因子IF2/eIF5B的X射线结构:对GDP和GTP结合的形态变化
A Roll-Mecak1, C Cao, T E Dever
1Laboratories of Molecular Biophysics The Rockefeller University 10021, New York, NY 10021, USA.
Cell
|December 15, 2000
概括
对通用翻译启动因子IF2/eIF5B的结构洞察力揭示了其杯状形状和GTPase功能. X射线结构揭示了IF2/eIF5B如何促进所有生命中蛋白质合成的关键步骤.
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:
- 通用翻译启动因子IF2/eIF5B对于启动生命所有三个领域的蛋白质合成至关重要.
- 它在连接核糖体子单元和促进启动者tRNA与核糖体结合方面发挥着至关重要的作用.
研究的目的:
- 阐明IF2/eIF5B的功能背后的结构机制.
- 确定IF2/eIF5B在不同功能状态 (自由,GDP绑定和GTP绑定) 中的三维结构.
主要方法:
- 采用X射线晶体学来获得高分辨率的结构.
- 使用比较结构分析来识别形状变化和功能元素.
主要成果:
- 该研究确定了IF2/eIF5B的X射线结构,其自由,不活跃的GDP结合形式和活跃的GTP结合形式.
- 确定了一个保存的域架构,包括N终端G域,EF-Tu型β桶,以及一个新的α/β/α三明治域.
- 揭示了一个分子杆机制,放大了从GTP结合部位到蛋白质的遥远区域的构造变化.
结论:
- 这些结构为IF2/eIF5B的GTPase活性及其在核糖体结合中的作用提供了机制基础.
- 这些发现提供了细菌,古生物和真核生物之间翻译启动的普遍机制的见解.
相关概念视频
GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Large G-proteins, also known...
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...
Coat Assembly and GTPases
Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
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...
Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...

