Turgay Research Projects
Protein homeostasis and stress response
We are investigating the control of protein homeostasis in the Gram-positive model organism Bacillus subtilis, especially when exposed to stress conditions such as heat or oxidative stress. Most of the highly conserved chaperone systems as well as AAA+ protease systems are present in the B. subtilis cellular protein quality control network. The proteolytic arm of the PQS entails AAA+ protease complexes, such as ClpCP, ClpXP, and ClpEP which can facilitate the general proteolysis of unfolded, misfolded and/or damaged proteins, which otherwise cannot be rescued or repaired by the chaperones. These AAA+ protease complexes can also be involved in regulatory proteolysis, by controlling e.g. the activity and stability of key transcription factors.
The substrate recognition and selection of the AAA+ proteins which are unfoldases often depends on their interaction with different adaptor proteins that can recognize and target substrate proteins to the AAA+ unfoldase such as ClpC. In the presence of the associated ClpP protease complex the unfolded substrate protein can be transferred for degradation by the ClpP protease complex. However, in the absence of ClpP, the same substrate protein can also refold, when released, allowing a possible switch between protein repair and removal.
We could identify the protein arginine kinase McsB, whose activity is induced by McsA and counteracted by the phosphatase YwlE, as the ClpC adaptor protein which is necessary to remove heat stress induced protein aggregates. We observed that this unusual chaperone system also allows decision between disaggregation and refolding or removal by degradation. Therefore, we are investigating the role of McsB, McsA, YwlE, ClpC & ClpP and cellular protein arginine phosphorylation in protein homeostasis, both in vivo and in vitro.
Heat Stress and Stringent Response
We are investigating the role of the second messenger (p)ppGpp and the stringent response during stress response and how this alarmone can limit and modulate translation. Here we are also applying genome-wide screening to approaches to identify genes involved in (p)ppGpp response during heat shock and other stresses.
During the biofilm formation in B. subtilis cells, specific matrix compounds are synthesized and secreted. The proteinaceous compound is the TasA protein, which can switch after secretion into different forms of fibrils stabilizing the extracellular matrix of the biofilm. In collaboration with the group of Hartmut Oschkinat at the Leibniz Forschungsinstitut für Molekular Pharmakologie (FMP, Berlin) and structural biologists in the Heinemann Lab at the Max Delbrück Center for Molecular Medicine (MDC, Berlin), we are continuing to investigate the molecular basis B. subtilis biofilm formation.