Arbeitsgruppe Prof. Turgay
Protein quality control systems are present in all cellular systems. They are essential to ensure cellular protein homeostasis (proteostasis) and monitor the folding and active state of proteins. These highly conserved systems include chaperones but also proteolytic machines, which can degrade misfolded and damaged protein species.
Disturbances in the interplay of chaperones and proteases by mutations or accumulation of misfolded, aggregated or amyloid proteins, can have serious and fatal consequences for cellular functions, as demonstrated for protein conformation diseases and aging.
Protein quality control may also play an important role in evolution due to the ability of chaperones to maintain and enable protein function even when mutations appear, resulting e.g. in changed protein sequence or expression levels.
The proteolytic systems involved in protein quality control, mostly AAA+ protease complexes such as ClpCP or ClpXP, are also involved in regulatory processes for example by controlled proteolysis of key regulatory proteins that are necessary for e.g. cellular developmental or differentiation processes.
We are interested in studying this important and terminal cellular decision to degrade a protein for both general and regulatory proteolysis. Therefore we want to investigate the mechanism of substrate selection together with the molecular mechanism of the ATP driven AAA+ protease complexes, responsible for the protein degradation. We use for our studies the Gram-positive model organism Bacillus subtilis, where the heat shock regulation and various other regulatory processes are comparably well characterized.
In the future, we are interested in further understanding the role of these proteases in general and regulatory proteolysis and the underlying molecular mechanism of these protease complexes. In particular, the activation, substrate selection and substrate recognition by ClpCP and its adaptor proteins are investigated with molecular biological, biochemical and genetic methods. We would like to understand how the protein arginine kinase McsB and MecA influence the activity of ClpC on the molecular level. Another research topic resulting from our experiments with McsB is the question about a more general role of McsB and its protein arginine kinase activity together with the cognate protein arginine phosphatase YwlE in the B. subtilis physiology especially during heat shock response and the possible influence of McsB on protein aggregate dynamics.
We want to examine and understand the response to stresses interfering with proteostasis on a molecular, cellular and population level. We want to explore the interplay, functional interaction and the cellular localization of the network of proteases and chaperones of the cellular protein quality control system and its dynamic interaction with protein aggregate formation.
- Bacillus subtilis
- general and regulatory proteolysis
- AAA+ protease complexes
- function and mechanism of ClpCP and its adaptor proteins
- function of the adaptor and protein arginine kinase McsB
- chaperones and protein quality control
- stress response and regulation
- interplay of chaperone and protease systems
- function of HSP90 (HtpG)