Molecular Role of 16S Ribosomal RNA in Translocation

描述(申请人提供)：蛋白质合成是一个基本的过程 在所有活着的有机体中。核糖体是核糖核蛋白复合体。 负责蛋白质合成。分子的最新原子分辨结构 大小核糖体亚基提供了一个独特的机会来理解 核糖体完成蛋白质合成这一复杂任务的机制。 蛋白质合成的延伸周期中的一个重要步骤是 TRNA-mRNA复合体的迭代运动，这一过程称为易位。在……里面 大肠杆菌，延伸因子G(EF-G)催化转位。这个 EF-G依赖易位的机制尚不清楚。长期的 我的实验室的目标是阐明易位的分子基础。 一些研究表明，核糖体RNAs(RRNAs)可能在 易位过程中的功能作用。我们最近写了一本小说 修改-干扰方法，允许我们检查 16S rRNA易位。该方法使用高效的特定于站点的 P位点结合的tRNA和16S rRNA之间的交叉连接以选择 移位活跃。我们将使用一种组合方法来识别 碱基、非桥联磷酸根和核糖2‘-羟基 对易位至关重要的rRNA。这项研究将提供信息 关于不容易获得的核糖体结构的动力学 X射线结晶学。 核糖体是几类抗生素灭活的靶标。 抗生素，如艾红霉素、壮观霉素、万古霉素、硫代链菌素和 氨基糖苷类化合物特别能抑制易位。其中一些 抗生素阻止16S rRNA经历结构变化 对易位至关重要。对抗生素有抗药性的细菌菌株 上升，导致这些感染的管理和治疗出现危机 在世界各地。了解易位的机制将提供 开发更有效的针对猪细小病毒核糖体的抗生素 这些耐药菌株的细菌。

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.