STRUCTURAL STUDIES OF REGULATION OF THE RIBOSOME

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在每个活着的有机体中，蛋白质的合成都是由一个名为核糖体的大型、动态的RNA-蛋白质大分子机器催化的。这个250万的道尔顿酶由两个不对称的亚基组成，它们促进信使RNA指导的遗传密码的翻译。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相互作用调节的结构基础感兴趣。我们感兴趣的一个问题是核糖体如何执行程序性和错误诱导的mRNA移码。我们最近的结构工作表明，框架移位tRNAs促进了A位点的非正则反密码子-密码子配对，我们的目标是将这些研究扩展到不同的修饰tRNAs，这些tRNAs在P位点形成肽键后。了解核糖体如何被调控的详细机制很重要，不仅因为翻译是所有细胞中的一个基本生物学过程，而且还因为许多临床相关的抗生素针对核糖体。此外，核糖体生物发生和翻译缺陷与多种疾病状态有关。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 problem 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.