STRUCTURAL STUDIES OF THE TRANSLATING RIBOSOME

翻译核糖体的结构研究

• 批准号: 8362423
• 负责人: Ji Zhu
• 金额: $ 0.38万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362423
• 关键词: Antibiotics; Base Sequence; Binding; Biological; Cells; Chemistry; Complex; Coupling; Evolution; Funding; Genetic; Genetic Code; Goals; Grant; Hydrolysis; Infection; Life; Messenger RNA; Molecular; National Center for Research Resources; Planets; Principal Investigator; Proteins; RNA; Radiation; Reading; Research; Research Infrastructure; Resolution; Resources; Ribosomes; Source; Structure; Terminator Codon; Transfer RNA; Translating; Translation Process Protein; Translations; United States National Institutes of Health; analog; base; chemical bond; combat; cost; design; microbial; molecular dynamics; novel; polypeptide; release factor; 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. The ribosome is the protein factory of the biological cell. It reads genetic information encoded in the nucleotide sequence of a messenger RNA strand, while synthesizing the corresponding polypeptide. The ribosome likely evolved in the ancient protocell on Earth and its structural core and essential enzymatic activities are universally conserved. Structural studies of the ribosome in its functional states are central in uncovering the molecular dynamics and chemistry of its functions, the chemistry of RNA and the evolution of life on the planet. Recently, we determined near-atomic crystal structures of release factor-bound ribosomal complexes captured at termination of translation. These structures provide the structural basis for stop codon recognition, peptidyl hydrolysis, coupling of decoding and hydrolysis, and principal aspects of the Genetic Code. Our immediate next goals are crystal structures of pre-, intermediate and post-termination complexes at the relevant resolution of chemical bonds. Also pressing are the determinations of crystal structures of a number of ribosomal states in translation, captured with pertinent tRNAs, mRNA, factors, substrate analogs and/or antibiotics. Together, these structures will provide ?molecular snapshots? of the processes of protein translation, and allow structure-based design of novel antibiotics combating microbial infections.

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。 核糖体是生物细胞的蛋白质工厂。它读取编码在信使RNA链的核苷酸序列中的遗传信息，同时合成相应的多肽。核糖体可能是在地球上的古老原始细胞中进化而来的，其结构核心和基本的酶活性是普遍保守的。核糖体在其功能状态下的结构研究是揭示其功能的分子动力学和化学，RNA的化学和地球上生命进化的核心。最近，我们确定了近原子的晶体结构的释放因子结合的核糖体复合物捕获在翻译终止。这些结构为终止密码子识别、肽基水解、解码和水解的偶联以及遗传密码的主要方面提供了结构基础。我们的下一个目标是在化学键的相关分辨率的前，中间和后终止复合物的晶体结构。同样紧迫的是确定翻译中的许多核糖体状态的晶体结构，这些状态被相关的tRNA、mRNA、因子、底物类似物和/或抗生素捕获。这些结构将提供？分子快照蛋白质翻译的过程，并允许基于结构的设计新的抗生素对抗微生物感染。