Function and mechanism of ClpV, a unique Hsp100 protein of proteobacteria that interacts with eukaryotic cells

• Applicant: Privatdozent Dr. Axel Mogk
• Subject Area: Biochemistry
• Term: from 2006 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 18878520

Hsp100 proteins form ring-shaped oligomers, which remodel target Substrates in an ATP dependent manner, an activity that is of central importance for cellular protein quality control. Most Hsp100 proteins (e.g. ClpA, ClpC, ClpX) associate with a peptidase (ClpP) and function in general and regulated proteolysis. In contrast, ClpB does not interact with ClpP but instead cooperates with the DnaK chaperone System in reactivating aggregated proteins. Functions and mechanisms of these major Hsp100 proteins have been studied in detail, however, little is known about specialized members of this protein family.We have recently identified a unique member of the Hsp100 protein family, ClpV, which is almost present in pathogenic but also in symbiotic proteobacteria. clpV is organized in a conserved gene cluster, exhibiting a similar organization as type in and type IV secretion Systems. ClpV, as well as members of the ClpV-associated gene cluster (CVAC) have not been characterized to date. The potential role of an Hsp100 protein in protein secretion and virulence is an exciting and an entirely new aspect for this protein family. We will use genetic and biochemical approaches to investigate ClpV function and mechanism with a major focus on the following aspects:1. Analysis of the regulation of clpV and its associated gene cluster.2. Investigation of the CVAC as a potential secretion System and analysis of ClpV function in this context.3. Analysis of the in vivo function of ClpV and the CVAC with a major focus on their putative roles in virulence.4. Identification of ClpV Substrates and partner proteins, which will be carried out in combination with a detailed structure-function analysis of this specialized Hsp100 protein.

• DFG Programme: Research Grants