Global characterization of the substrate spectrum of the Corynebacterium glutamicum Clp protease

• Applicant: Dr. Steffen Schaffer
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: from 2004 to 2006
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5422806

ATP-dependent proteases are important cellular tools for removing non-functional proteins from bacterial cells. Moreover, these enzymes perform important regulatory roles by modulating the concentration of certain functional proteins via conditional degradation. Such conditional substrates are often key components of regulatory or metabolic pathways involved in, e.g. cell differentiation, amino acid biosynthesis and pathogenesis. Our work will focus on the Corynebacterium glutamicum Clp protease. This bacterium is of considerable biotechnological importance and serves as model organism for closely related pathogens such as C. diphtheriae and Mycobacterium tuberculosis. We attempt to comprehensively identify the conditional substrate spectra of the C. glutamicum ClpCP, ClpEP and ClpXP proteases. The function of the identified substrates will provide us with first indications which physiological processes are subject to Clp-dependent regulation in this organism and, possibly, its pathogenic relatives. Moreover, we will be enabled to compare the substrate specificities of alternative Clp holoenzymes and to detect possible overlaps. Subsequently, we want to identify sequence determinants within selected Clp protease substrates required for conditional degradation by ClpCP, ClpEP or ClpXP. The data obtained will be of general importance for understanding, i) to which extent proteolysis contributes to regulatory processes in bacteria, and ii) the molecular basis of substrate recognition/discrimination by Clp proteases.Die Projektleitung hat hat Herr Professor Dr. Michael Bott überneommen.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1132: Proteolysis in Prokaryotes: Protein Quality Control and Regulatory Principle
• Participating Person: Professor Dr. Michael Bott