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: 6623097
• 负责人: SIMPSON JOSEPH
• 金额: $ 20.91万
• 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/6623097
• 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（由申请人提供）：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 负责蛋白质的合成。最近的原子分辨率结构 大小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复杂任务的机制。 蛋白质合成延伸循环中的重要步骤之一是 tRNA-mRNA 复合物的迭代运动，这个过程称为易位。在 大肠杆菌的延伸因子 G (EF-G) 催化易位。这 EF-G 依赖性易位机制尚不清楚。长期来看 我实验室的目标是阐明易位的分子基础。 多项研究表明，核糖体 RNA (rRNA) 可能发挥着重要作用 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 易位。该方法使用高效的位点特异性 P位点结合的tRNA和16S rRNA之间的交联以选择核糖体 易位活跃。我们将使用组合方法来识别 16S 内的碱基、非桥磷酸氧和核糖 2'-羟基 对于易位至关重要的 rRNA。这项研究将提供信息 关于无法轻易获得的核糖体结构的动力学 X射线晶体学。 核糖体是几类抗生素失活的目标。 抗生素如红霉素、大观霉素、紫霉素、硫链丝菌素等 氨基糖苷类特异性抑制易位。其中一些 抗生素可防止 16S rRNA 发生结构变化 对于易位至关重要。抗生素耐药菌株已在 上升，导致这些感染的管理和治疗危机 全世界。了解易位机制将提供 开发针对核糖体的更有效抗生素的见解 这些耐药菌株。