STRUCTURAL STUDIES OF RIBOSOME REGULATION

核糖体调控的结构研究

• 批准号: 8361672
• 负责人: Christine M Dunham
• 金额: $ 8.75万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361672
• 关键词: Antibiotics; Anticodon; Biogenesis; Biological Process; Cells; Codon Nucleotides; Defect; Disease; Enzymes; Funding; Genetic Code; Grant; Laboratories; Life; Messenger RNA; National Center for Research Resources; Organism; Peptides; Principal Investigator; Protein Biosynthesis; Proteins; RNA; RNA-Protein Interaction; Regulation; Research; Research Infrastructure; Resources; Ribosomes; Site; Source; Transfer RNA; Translations; United States National Institutes of Health; Work; base; clinically relevant; cost; dalton; interest; programs; structural biology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In every living organism, protein synthesis is catalyzed by a large, dynamic RNA-protein macromolecular machine called the ribosome. This 2.5 million Dalton enzyme is comprised of two asymmetric subunits that promote messenger RNA-directed translation of the genetic code. Our laboratory is interested in the structural basis for how protein synthesis is regulated via protein-protein and protein-RNA interactions. One aspect of regulation we are interested in is how the ribosome performs both programmed and error-inducing mRNA frameshifts. Our recent structural work shows that frameshifts tRNAs promote non-canonical anticodon-codon pairing in the A site and we aim to expand these studies to different modified tRNAs after peptide bond formation in the P site. Understanding the detailed mechanism of how the ribosome is regulated is important not only because translation is a fundamental biological process in all cells, but also because many clinically relevant antibiotics target the ribosome. Additionally defects in ribosome biogenesis and translation are implicated in wide variety of disease states.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 在每一个生物体中，蛋白质的合成都是由一个叫做核糖体的大型动态RNA-蛋白质大分子机器催化的。这种250万道尔顿的酶由两个不对称亚基组成，它们促进信使RNA指导的遗传密码翻译。我们的实验室对蛋白质合成如何通过蛋白质-蛋白质和蛋白质-RNA相互作用进行调节的结构基础感兴趣。我们感兴趣的一个方面是核糖体如何执行程序化和错误诱导mRNA移码。我们最近的结构工作表明，移码tRNA促进非典型的反密码子-密码子配对的A网站，我们的目标是扩大这些研究不同的修饰后的tRNA在P网站的肽键形成。理解核糖体如何被调节的详细机制是重要的，不仅因为翻译是所有细胞中的基本生物学过程，而且因为许多临床相关的抗生素靶向核糖体。此外，核糖体生物合成和翻译的缺陷与各种疾病状态有关。