|
Unicellular organisms like bacteria or yeast are particularly exposed to detrimental environmental growth conditions triggering protein unfolding and aggregation. Stress resistance is mediated by a protein quality control (PQC) system which target misfolded and aggregated protein species to degradation or refolding pathways. We are working on central players of bacterial and fungal PQC systems including refolding and degrading AAA+ machines. We study how they mechanistically work and how they are regulated, ensuring high activities during stress conditions while protecting the cellular proteome from unwanted and harmful actions at physiological conditions.
E. coli cells harboring stress-induced protein aggregates
Current Projects
-
Novel bacterial disaggregases provide extreme heat resistance
-
sHsp sequestrases: mechanism and interplay with protein disaggregases
-
The central ClpC/ClpP protease as antibacterial drug target
-
PQC and the heat shock response in yeast cells
Selected
publications
Original
Papers
Bohl, V., Hollmann, N.M., Melzer, T., Katikaridis, P., Meins, L., Simon, B., Flemming, D., Sinning, I., Hennig, J., and Mogk, A. (2024). The Listeria monocytogenes persistence factor ClpL is a potent stand-alone disaggregase. eLife 12. 10.7554/eLife.92746.
Katikaridis, P., Simon, B., Jenne, T., Moon, S., Lee, C., Hennig, J., and Mogk, A. (2023). Structural basis of aggregate binding by the AAA+ disaggregase ClpG. J Biol Chem 299, 105336. 10.1016/j.jbc.2023.105336.
Shrivastava, A., Sandhof, C.A., Reinle, K., Jawed, A., Ruger-Herreros, C., Schwarz, D., Creamer, D., Nussbaum-Krammer, C., Mogk, A., and Bukau, B. (2022). The cytoprotective sequestration activity of small heat shock proteins is evolutionarily conserved. J Cell Biol 221. 10.1083/jcb.202202149.
Taylor, G., Frommherz, Y., Katikaridis, P., Layer, D., Sinning, I., Carroni, M., Weber-Ban, E., and Mogk, A. (2022). Antibacterial peptide CyclomarinA creates toxicity by deregulating the Mycobacterium tuberculosis ClpC1-ClpP1P2 protease. J Biol Chem 298, 102202. 10.1016/j.jbc.2022.102202.
Ho, C.T., Grousl, T., Shatz, O., Jawed, A., Ruger-Herreros, C., Semmelink, M., Zahn, R., Richter, K., Bukau, B., and Mogk, A. (2019). Cellular sequestrases maintain basal Hsp70 capacity ensuring balanced proteostasis. Nature communications 10, 4851. 10.1038/s41467-019-12868-1.
Maurer, M., Linder, D., Franke, K.B., Jager, J., Taylor, G., Gloge, F., Gremer, S., Le Breton, L., Mayer, M.P., Weber-Ban, E., Carroni, M., Bukau, B., Mogk, A. (2019). Toxic Activation of an AAA+ Protease by the Antibacterial Drug Cyclomarin A. Cell Chem Biol 26, 1169-1179 e1164. 10.1016/j.chembiol.2019.05.008.
Lee, C., Franke, K.B., Kamal, S.M., Kim, H., Lunsdorf, H., Jager, J., Nimtz, M., Trcek, J., Jansch, L., Bukau, B., Mogk, A., Römling, U. (2018). Stand-alone ClpG disaggregase confers superior heat tolerance to bacteria. Proc Natl Acad Sci U S A 115, E273-E282. 10.1073/pnas.1712051115.
Carroni, M., Franke, K.B., Maurer, M., Jager, J., Hantke, I., Gloge, F., Linder, D., Gremer, S., Turgay, K., Bukau, B., and Mogk, A. (2017). Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control. eLife 6. 10.7554/eLife.30120.
|
