Structural Basis of Antitermination by the E. coli Phages lambda and HK022

• Applicants: Professor Dr. Paul Rösch; Professor Dr. Markus C. Wahl
• Subject Area: Structural Biology
• Term: from 2006 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 22565507

The current grant application describes a unique 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 a very fundamental transcription regulatory process in the bacterium Escherichia coli (E. coli) that has analogs in eukaryotes. Modulation of transcription termination and antitermination is an essential regulatory mechanism of the replication of a large number of viruses including the prototypical E. coli phage ¿, the E. coli phage Hongkong 022 (HK022), the eukaryotic immunodeficiency viruses such as human immunodeficiency virus 1 (HIV-1) as well as a number of other viruses. The current application targets the three-dimensional structure of the termination/ antitermination systems of phage ¿/ E. coli and of HK022/ E. coli. The long-term goal is to extend our knowledge of the basis of transcription regulation by antitermination in prokaryotes, with the eventual goal of rationally designing new antibiotics, and to provide a basis for the rational design of drugs against lentiviruses. In particular, we propose to determine major parts of the three-dimensional structure of the complete phage ¿/ E. coli antitermination and the phage HK022/ E. coli termination complex. Besides phage-encoded antitermination proteins ¿N and Nun, respectively, and regulatory RNA elements, the key regulator proteins in these complexes are NusA and NusG, on which our studies are focused on.

• DFG Programme: Research Grants
• Major Instrumentation: Cooling unit for the 700 MHz cryoprobe
• Instrumentation Group: 1790 Spektrometer (Massen-, NMR-, außer 170-178)
• Participating Person: Professorin Dr. Birgitta Maria Wöhrl