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Projekt
Global regulation by proteolysis in Escherichia coli: Molecular recognition, signal integration and quantitative analysis of proteolysis-controlled regulatory circuits
Antragstellerin
Professorin Dr. Regine Hengge
Fachliche Zuordnung
Stoffwechselphysiologie, Biochemie und Genetik der Mikroorganismen
Förderung
Förderung von 2002 bis 2009
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5360932
The cellular amount of certain key regulatory factors is the result of a highly dynamic and regulated balance between regulation of synthesis and degradation. Using the multiple stress-inhibited proteolysis of the Sigma-S subunit of RNA polymerase in E.coli as a model system, the proposal submitted here focusses on the two major unsolved problems in the field of regulated proteolysis: (i) the molecular details of selective substrate recognition by the proteolytic machinery, and (ii) the signal transduction pathways that connect environmental stress conditions to the rate of proteolysis of a key cellular regulator. Sigma-S is directly targeted by a recognition factor, RssB, whose affinity for a small region within Sigma-S (a2.5) is controlled by phosphorylation. RssB then transfers Sigma-S to the ClpXP protease, where Sigma-S is rapidly and completely degraded. Molecular interactions between proteolytic recognition sites in Sigma-S (and probably in Sigma-70) and various recognizing factors and chaperones (RssB, ClpX, ClpA) will be studied. In addition, the signal transduction pathways that inhibit Sigma-S turnover in response to various stress conditions will be elucidated. These pathways either control RssB phosphorylation and/or the cellular amount of and interaction with competing binding partners for Sigma-S and ClpXP, such as core RNA polymerase or alternative ClpXP substrates, respectively. These studies should provide important novel insights into regulated proteolysis as well as into complex bacterial signal integration networks in general.
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