GENETIC APPROACHES TO PROTEIN-NUCLEIC ACID INTERACTIONS

描述：该项目使用了分子生物学和 遗传学来研究翻译设备的两个组件，这两个组件是 对遗传密码的规则负责。这些组件--转移RNA (TRNAs)和氨基酰tRNA合成酶--在进化和 成为所有生命形式的必需品。该代码是在氨基酰化反应中建立的。 反应，二十种氨基酸中的每一种都与其同源物相连 携带该氨基酸的反密码子三联体的tRNA。那里 典型的是每种氨基酸都有一个不同的合成酶。在拟议的工作中， 很多工作都是针对使用遗传方法来研究罚款是如何 氨基酸的结构识别是通过tRNA合成酶实现的。这 高度的歧视对于建立和维持 代码的准确性。对于某些酶来说，同源trna起着关键作用。 在实现这种高度分化的精细结构歧视中的作用 非常相似的氨基酸。TRNA的作用是引导一种失活的 从活性部位到第二个编辑部位的氨基酸，在那里一个潜在的 消除了氨酰化反应的误差。遗传方法被提出用来 探索编辑中心突变在体内的后果，并 证明氨基酸在蛋白质中的错误结合 在细胞内合成。在进一步的工作中，半人工tRNA合成酶将 在体内被创造和研究。这项工作的目的是提供对 如何从简单的片段组装特定的氨基酰化系统。 最后，最近的工作确定了tRNA合成酶在高等 生物体，尤其是在人类细胞中。这些角色将被调查 进一步使用基因筛查。 因为trna合成酶是必需的蛋白质，所以它们被作为 新一类抗生素的目标。此外，最近的示威活动 这些蛋白质在细胞信号机制中的新作用表明 其他与健康相关的应用程序将随着更多基本信息的出现而出现 在这些系统上获得的。

DESCRIPTION: This project uses methods and logic of molecular biology and genetics to investigate two components of the translation apparatus that are responsible for the rules of the genetic code. These components--transfer RNAs (tRNAs) and aminoacyl tRNA synthestases-- appeared early in evolution and became essential for all life forms. The code is established in aminoacylation reactions, whereby each of the twenty amino acids is attached to its cognate tRNA that bears the anticodon triplet of the code for that amino acid. There typically is one distinct synthetase for each amino acid. In the proposed work, much effort is directed at using genetic approached to study how the fine structure recognition of amino acids is achieved by the tRNA synthetases. This high level of discrimination is essential for establishing and maintaining the accuracy of the code. For some of the enzymes, the cognate tRNA plays a key role in achieving this highly differentiated fine structure discrimination of closely similar amino acids. The role of the tRNA is to direct a misactivated amino acid from the active site to a second, editing site, where a potential error of aminoacylation is eliminated. Genetic approaches are proposed to explore the consequences in vivo of mutations in the center for editing, and to demonstrate the misincorporation of amino acids into proteins as they are synthesized in the cell. In further work, semi-artificial tRNA synthetases will be created and studied in vivo. This work is intended to provide insight into how specific systems of aminoacylation can be assembled from simple pieces. Finally, recent work has established other roles for tRNA synthetases in higher organisms, particularly in human cells. These roles are to be investigated further using genetic screens. Because tRNA synthetases are essential proteins, they are being pursued as targets for new classes of antibiotics. Moreover, the recent demonstration of novel roles for these proteins in cellular signaling mechanisms suggests that other heath-related applications will emerge as more basic information is obtained on these systems.