NMR ANALYSIS OF RNA IN THE PEPTIDYL TRANSFERASE CENTER

蛋白质翻译，由核糖体催化，是最好的- 保守的大分子复合物，是所有生物的基本特征， 有机体越来越多的证据表明， 形成主要由核糖体RNA（rRNS）介导，其提供了一种 必要的催化核心，称为肽基转移酶中心（PTC）， 对于这个功能。 该建议的重点是rRNA元件的三级结构， PTC在遗传和生化方面都与 肽基转移的功能。NMR分析结合 分子动力学计算将被用于导出解决方案 RNA分子的结构模型。NMR中的长度限制 本研究还将研究RNA分子的分析， 特别是通过使用氘代RNA作为磁性“沉默”， 关键RNA元件的上下文。野生型结构比较 PTC序列和突变体序列，已知损害肽基 转移酶功能，将允许识别关键结构 元素，必要的生物活性的肽键形成。

Protein translation, catalyzed by the ribosome, one of the most well- conserved macromolecular complexes, is a basic feature of all living organisms. Evidence has been accumulating that catalysis of peptide bond formation is mediated primarily by ribosomal RNA (rRNS), which provides a requisite catalytic core, known as the peptidyl transferase center (PTC), for this function. This proposal focuses on the tertiary structure of rRNA elements within the PTC that have been both genetically and biochemically implicated in the function of peptidyl transfer. NMR analysis in combination with molecular dynamics calculations will be utilized to derived solution structural models of RNA molecules from this domain. Length limits in NMR analysis of RNA molecules will also be investigated in this study, in particular through the use of deuterated RNA as a magnetically 'silent' context for a key RNA element. Comparison between structures of wild type PTC sequence and mutant sequences, known to compromise peptidyl transferase function, will allow identification of key structural elements, necessary for the biological activity of peptide bond formation.