Crystal Structure of the Ribosome

描述(申请人提供)：核糖体是负责在所有活细胞中翻译遗传密码和合成蛋白质的分子复合体。这个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的合成。这项建议旨在获得核糖体功能络合物的晶体，并通过X射线结晶学解决其结构。这些结果将与从生化、生物物理和遗传学方法获得的核糖体功能知识结合起来，重建蛋白质合成过程的动态、三维描述。公共卫生相关性由于细菌核糖体是许多强大的抗菌素的靶标，对其结构和功能的深入了解将有助于设计新药来对抗日益严重的耐药病原菌问题。与公共健康密切相关的还有一项发现，人类线粒体核糖体的突变导致了包括耳聋和癌症在内的各种人类疾病。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.