Crystal Structure of the Ribosome

描述（由申请人提供）：核糖体是所有活细胞中负责遗传密码翻译和蛋白质合成的分子复合物。该项目的最终目标是从核糖体及其与信使RNA、转移RNA和蛋白质合成因子的相互作用方面了解蛋白质合成。本课题旨在获得核糖体功能复合物的晶体，并利用x射线晶体学方法解析其结构。这些结果将与从生化、生物物理和遗传方法获得的核糖体功能知识相结合，重建蛋白质合成过程的动态、三维描述。由于细菌核糖体是许多强效抗菌抗生素的靶标，因此对其结构和功能的更深入了解将有助于设计新药，以对抗日益严重的耐药致病菌问题。人类线粒体核糖体的突变是多种人类疾病的原因，包括耳聋和癌症，这一发现也与公共卫生密切相关。对核糖体结构和功能的研究可以提高我们对这些分子缺陷如何导致疾病的理解，为设计治疗方法提供坚实的基础。

DESCRIPTION (provided by applicant): Ribosomes are the molecular complexes that are responsible for translation of the genetic code and synthesis of proteins in all living cells. The ultimate goal of this project is to obtain an understanding of protein synthesis in terms of the ribosome and its interactions with messenger RNA, transfer RNA and the protein synthesis factors. This proposal aims to obtain crystals of functional complexes of the ribosome and to solve their structures by x-ray crystallography. These results will be combined with knowledge of ribosome function obtained from biochemical, biophysical and genetic approaches to reconstruct a dynamic, three-dimensional description of the process of protein synthesis. PUBLIC HEALTH RELEVANCE Since bacterial ribosomes are the targets of many powerful antimicrobial antibiotics, a deeper understanding of their structure and function will help to design new drugs to combat the increasing problem of drug-resistant pathogenic bacteria. Also of great relevance to public health is the finding that mutations in human mitochondrial ribosomes are responsible for a variety of human diseases, including deafness and cancer. Research on ribosome structure and function can improve our understanding of how these molecular defects lead to disease, providing a solid basis for devising approaches to design of therapies.