Molecular Role of 16S Ribosomal RNA in Translocation

16S 核糖体 RNA 在易位中的分子作用

• 批准号: 6462889
• 负责人: SIMPSON JOSEPH
• 金额: $ 20.95万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6462889
• 关键词: Escherichia coli; bacterial RNA; bacterial genetics; cell component structure /function; chemical structure function; crosslink; genetic translation; intermolecular interaction; messenger RNA; model design /development; molecular dynamics; nucleic acid sequence; nucleic acid structure; nucleotide analog; physical model; protein biosynthesis; ribosomal RNA; ribosomes; structural biology; transfer RNA

DESCRIPTION (provided by applicant): Protein synthesis is a fundamental process in all living organisms. Ribosomes are the ribonucleoprotein complexes responsible for protein synthesis. Recent atomic resolution structures of the large and small ribosomal subunits provide a unique opportunity to understand the mechanism by which ribosomes perform the complex task of protein synthesis. One of the important steps in the elongation cycle of protein synthesis is the iterative movement of the tRNA-mRNA complex, a process called translocation. In Escherichia coli, elongation factor G (EF-G) catalyzes translocation. The mechanism of EF-G-dependent translocation is poorly understood. The long-term goal of my laboratory is to elucidate the molecular basis of translocation. Several lines of studies indicate that the ribosomal RNAs (rRNAs) may play a functional role during translocation. We recently developed a novel modification-interference approach that will permit us to examine the role of 16S rRNA in translocation. The method uses a highly efficient site-specific cross-link between P site bound tRNA and 16S rRNA to select ribosomes that are active in translocation. We will use a combinatorial approach for identifying bases, non-bridging phosphate oxygens, and ribose 2'-hydroxyl groups within 16S rRNA that are critical for translocation. This study will provide information about the dynamics of ribosome structure that cannot be easily acquired by X-ray crystallography. Ribosomes are the target for inactivation by several classes of antibiotics. Antibiotics such as eiythromycin, spectionmycin, viomycin, thiostrepton, and the aminoglycosides specifically inhibit translocation. Some of these antibiotics prevent the 16S rRNA from undergoing structural changes that are critical for translocation. Antibiotic-resistant strains of bacteria are on the rise, causing a crisis in the management and treatment of these infections throughout the world. Understanding the mechanism of translocation will provide insights for developing more effective antibiotics that target the ribosome of these drug-resistant strains of bacteria.

描述（申请人提供）：蛋白质合成是一个基本过程 在所有生物体中。核糖体是核糖核蛋白复合物 负责蛋白质合成。最近的原子分辨率结构 大小的核糖体亚基提供了一个独特的机会来理解 核糖体执行蛋白质合成的复杂任务的机制。 蛋白质合成伸长周期的重要步骤之一是 tRNA-mRNA复合物的迭代运动，这一过程称为易位。在 大肠杆菌，伸长因子G（EF-G）催化易位。这 EF-G依赖性易位的机制知之甚少。长期 我的实验室的目标是阐明易位的分子基础。 几条研究表明，核糖体RNA（RRNA）可能会发挥作用 易位过程中的功能作用。我们最近开发了一本小说 修改干扰方法将使我们能够检查 16S rRNA在易位中。该方法使用高效的网站特异性 p位点结合的tRNA和16S rRNA之间的交联，以选择核糖体 活跃的易位。我们将使用一种组合方法来识别 碱基，非桥接磷酸盐氧和核糖2'-羟基在16s之内 rRNA对于易位至关重要。这项研究将提供信息 关于核糖体结构的动力学，无法轻易获取 X射线晶体学。 核糖体是几种抗生素失活的靶标。 抗生素，例如Eiythromycin，spectionmycin，Viomycin，Thiostrepton和 氨基糖苷特别抑制易位。其中一些 抗生素阻止16S rRNA发生结构变化 对易位至关重要。抗生素耐药菌的细菌菌株在 崛起，在这些感染的管理和治疗中造成危机 全世界。了解易位机制将提供 开发更有效抗生素的见解，以靶向核糖体 这些耐药菌株的细菌菌株。