Transcription in E. coli: Structural Basis of Nus-Factor Dependent Regulation

当前的拨款申请描述了X射线晶体学、核磁共振光谱学和分子动力学计算、光谱学和生化方法相结合的努力，以揭示大肠杆菌（E. coli）转录调节过程的结构基础。coli）。转录起始、延伸、终止和抗终止的调控是包括原型大肠杆菌在内的许多病毒增殖的重要调控机制。coli噬菌体λ、E.大肠杆菌噬菌体香港022（HK 022）、真核慢病毒如人免疫缺陷病毒1（HIV-1）以及许多其它病毒。本申请靶向E.大肠杆菌的Nus因子，特别是这些调控过程的构象基础。同时，对λ/ E. coli抗终止系统和HK 022/ E. coli终止系统进行研究。长期目标是扩展我们对原核生物转录调控及其调节可能性的认识，最终目标是合理设计新的抗生素。

The current grant application describes an effort towards the combination of X-ray crystallography, NMR-spectroscopy and molecular dynamics calculations, optical spectroscopy and biochemical methods to shed light onto the structural basis of transcription regulation process in the bacterium Escherichia coli (E. coli). Modulation of transcription initiation, elongation, termination and antitermination is an essential regulatory mechanism of the propagation of a large number of viruses including the prototypical E. coli phage λ, the E. coli phage Hong Kong 022 (HK022), the eukaryotic lentiviruses such as human immunodeficiency virus 1 (HIV-1) as well as a number of other viruses. The current application targets the regulation of transcription in E. coli by the Nus-factors, in particular the conformational basis of these regulatory processes. In parallel, the mechanism of the phage λ/ E. coli antitermination system and the HK022/ E. coli termination system will be studied. The long-term goal is to extend our knowledge of transcription regulation and possibilities of its modulation in prokaryotes, with the eventual goal of rationally designing new antibiotics.