GENETIC APPROACHES TO PROTEIN/NUCLEIC ACID INTERACTIONS

蛋白质/核酸相互作用的遗传学方法

• 批准号: 2625635
• 负责人: PAUL R SCHIMMEL
• 金额: $ 14.89万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-03-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2625635
• 关键词: Escherichia coli; Saccharomyces cerevisiae; aminoacid tRNA ligase; biochemical evolution; enzyme activity; gene mutation; genetic manipulation; human genetic material tag; hybrid enzyme; nucleic acid sequence; protein engineering; site directed mutagenesis; thermophilic organism; transfer RNA

This project explores protein-RNA interactions which are at the heart of the genetic code. Aminoacyl transfer RNA synthetases are enzymes found in all life forms and which are thought to be among the earliest proteins to appear. They catalyze attachment of amino acids to transfer RNAs which harbor the trinucleotides of the code. In this work, genetic approaches are used to understand the high specificity of the synthetase-tRNA interactions on which the code is dependent. The systems under investigation include bacterial, yeast and human enzymes and tRNAs. Specific projects include genetic manipulations to convert one synthetase into another, genetic engineering to enable a synthetase to switch its species specificity, manipulation of a synthetase to achieve a subtle change in the way that it recognizes atoms in the RNA minor groove, and determination of the specialized RNA recognition features of a human mitochondrial tRNA synthetase. Understanding of protein-RNA interactions in this system is broadly useful for understanding protein-RNA interactions in general. The disruption and alternation of specific RNA- protein interactions is a possible basis for developing therapeutic agents for treatment of human diseases.

该项目探讨了蛋白质-RNA相互作用，这是核心的 遗传密码 氨酰基转移RNA合成酶是在大肠杆菌中发现的酶。 所有的生命形式，被认为是最早的蛋白质， 出现 它们催化氨基酸与转移RNA的连接， 含有密码的三核苷酸 在这项工作中，遗传方法 用于理解合成酶-tRNA的高度特异性 代码所依赖的交互。 中的系统 研究包括细菌、酵母和人类酶和tRNA。 具体项目包括基因操作， 另一个是基因工程，使合成酶能够转换它的 物种特异性，操纵合成酶以实现微妙的 改变了它识别RNA小沟中原子的方式， 确定人的特异性RNA识别特征 线粒体tRNA合成酶。 蛋白质-RNA相互作用 在这个系统中广泛地用于理解蛋白质-RNA 一般的互动。 特定RNA的破坏和改变- 蛋白质相互作用是开发治疗剂的可能基础 用于治疗人类疾病。