Structural and functional studies on biological macromolecules involved in the flow of genetic information and the cellular signal transduction.

参与遗传信息流动和细胞信号转导的生物大分子的结构和功能研究。

基本信息

批准号：
15107002
负责人：
YOKOYAMA Shigeyuki
金额：
$ 71.3万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (S)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2007
项目状态：
已结题

项目摘要

To understand in detail the systems of genetic expression and cellular signal transduction, which consist of cascades of macromolecular interactions, molecular interactions involved in the cascades were analyzed at atomic resolutions by crystallography. We targeted post-transcriptional tRNA processing and modification enzymes and aminoacyl-tRNA synthetases, which are responsible for accurate joining tRNA and amino acid during translation, and performed structural analyses of their complexes with tRNAs, other substrates, and/or inhibitors. We also determined the crystal structure of Vasa, an RNA helicase involved in the differentiation of Drosophila germline, and elucidated structural basis of the RNA double strand resolution by a DEAD-box RNA helicase. Furthermore, we succeeded in crystal structure determination of RNA polymerase and Dmc1, which play central roles in transcription and homologous recombination in meiosis, respectively. The structural information was applied to develop the artificial genetic code system to incorporate a useful, natural or non-natural amino acid into a specific position of any protein. We have established systems to incorporate tyrosine or lysine derivatives, and thus opened a way to the technology that facilitates incorporating an amino acid possessing fluorescent, reactive, or heavy-atom containing groups.

为了详细了解由大分子相互作用组成的遗传表达和细胞信号转导系统，通过晶体学在原子分辨率下分析了级联反应的分子相互作用。我们靶向转录后TRNA加工和修饰酶和氨基酰基-TRNA合成酶，这些酶负责在翻译过程中准确连接tRNA和氨基酸，并与TRNA，其他底物和/或抑制剂对其复合物进行了结构分析。我们还确定了VASA的晶体结构，VASA是参与果蝇种系的分化的RNA解旋酶，以及通过死盒RNA解旋酶阐明RNA双链分辨率的结构基础。此外，我们在RNA聚合酶和DMC1的晶体结构测定方面取得了成功，它们分别在减数分裂中的转录和同源重组中起着核心作用。将结构信息应用于开发人工遗传密码系统，以将有用的，自然或非天然氨基酸纳入任何蛋白质的特定位置。我们已经建立了结合酪氨酸或赖氨酸衍生物的系统，因此为促进具有荧光，反应性或重原子组的氨基酸的技术打开了一种方法。

项目成果

期刊论文数量（184）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Crystal structure of the hypothetical protein TTHA1013 from Thermus thermophilus HB8

DOI：
10.1002/prot.20692
发表时间：
2005-12
期刊：
Proteins: Structure
影响因子：
0
作者：
M. Hattori;E. Mizohata;M. Manzoku;Y. Bessho;K. Murayama;T. Terada;S. Kuramitsu;M. Shirouzu;S. Yokoyama
通讯作者：
M. Hattori;E. Mizohata;M. Manzoku;Y. Bessho;K. Murayama;T. Terada;S. Kuramitsu;M. Shirouzu;S. Yokoyama

Human centromere protein B induces translational positioning of nucleosomes on alpha-satellite sequences

人类着丝粒蛋白 B 诱导核小体在 α 卫星序列上的翻译定位