ZMB Member Michael Ehrmann
ZMB Member
Michael Ehrmann
Next ZMB-Member
Prof. Dr. Michael Ehrmann
Faculty of Biology
Center of Medical Biotechnology (ZMB)
University of Duisburg-Essen
Universitätsstr. 2
45141 Essen
- +49 201 183 2949
- Website
- Selected Publications
- Publication Metrics
- ZMB Research Program
Molecular and Chemical Cell Biology
Research Overview
Mechanism and Translational Aspects of Protein Quality Control
Each cell hosts thousands of different proteins that vary greatly in copy number and in their chemical properties. Despite this complication, nature has evolved efficient mechanisms of quality control to ensure that all proteins are biologically active, localised to the proper cellular compartment and present in appropriate quantity. This functional state must be maintained under normal as well as under stress conditions. The failure of quality control can influence cell growth and can cause severe diseases ranging for example from bacterial infections to neurodegenerative and arthritic diseases or cancer.
We are studying evolutionarily conserved cellular factors that are involved in key aspects of quality control, such as detection of misfolded proteins, signal recognition and integration into the unfolded protein response pathways and regeneration of the functional state. These studies aim at revealing the general concepts governing the underlying molecular mechanisms of protein diagnosis, repair and degradation.
The focus of our research is on the widely conserved HtrA family of serine proteases that are involved in all aspects of ATP-independent protein quality control. We showed that a protein can combine the antagonistic functions of chaperone and protease activities within a single polypeptide. Furthermore, in collaboration with Tim Clausen (IMP Vienna), it was shown that HtrAs can switch between various oligomeric states and the mechanism of activation by oligomerisation has been elucidated. In recent years, work on human HTRA1 has revealed its involvement in cancer (as a tumor suppressor), in arthritis (by remodelling of the extracellular matrix) and in Alzheimer's disease (by degrading proteins and protein fragments that aggregate to form senile plaques).
Since a number of years we are using chemical biology approaches, mainly in collaboration with Markus Kaiser (Uni Duisburg-Essen), Biotech and Pharmaceutical companies to generate tools for basic research and for drug development purposes. In addition, the structure of HTRA1 with a bound inhibitor provides leads for the search of HTRA1 modulators that are of therapeutic relevance.
Read more
Selected Publications
-
Determinants of amyloid fibril degradation by the PDZ protease HTRA1In: Nature Chemical Biology Vol. 11 (2015) Nr. 11, pp. 862 - 869Online Full Text: dx.doi.org/ Online Full Text (Open Access)
-
XCtpB assembles a gated protease tunnel regulating cell-cell signaling during spore formation in bacillus subtilisIn: Cell Vol. 155 (2013) Nr. 3, pp. 647 - 658Online Full Text: dx.doi.org/
-
Newly folded substrates inside the molecular cage of the HtrA chaperone DegQIn: Nature Structural & Molecular Biology Vol. 19 (2012) Nr. 2, pp. 152 - 157Online Full Text: dx.doi.org/
-
HTRA proteases : regulated proteolysis in protein quality controlIn: Nature Reviews Molecular Cell Biology Vol. 12 (2011) Nr. 3, pp. 152 - 162Online Full Text: dx.doi.org/
-
Protein quality control in the bacterial periplasmIn: Annual Review of Microbiology Vol. 65 (2011) pp. 149 - 168Online Full Text: dx.doi.org/
-
Structural adaptation of the plant protease Deg1 to repair photosystem II during light exposureIn: Nature Structural & Molecular Biology Vol. 18 (2011) Nr. 6, pp. 728 - 731Online Full Text: dx.doi.org/
-
Substrate induced remodeling of the active site regulates human HtrA1 activityIn: Nature Structural & Molecular Biology Vol. 18 (2011) pp. 386 - 388Online Full Text: dx.doi.org/
-
Determinants of structural and functional plasticity of a widely conserved protease chaperone complexIn: Nature Structural & Molecular Biology Vol. 17 (2010) Nr. 7, pp. 837 - 843Online Full Text: dx.doi.org/
-
Determinants of regulated proteolysis in signal transductionIn: Genes and Development Vol. 21 (2007) Nr. 1, pp. 6 - 10Online Full Text: dx.doi.org/
-
Regulation of the σE stress response by DegS: How the PDZ domain keeps the protease inactive in the resting state and allows integration of different OMP-derived stress signals upon folding stressIn: Genes and Development Vol. 21 (2007) Nr. 20, pp. 2659 - 2670Online Full Text: dx.doi.org/
-
Crystal structure of the DegS stress sensor: How a PDZ domain recognizes misfolded protein and activates a proteaseIn: Cell Vol. 117 (2004) Nr. 4, pp. 483 - 494
-
Proteolysis as a regulatory mechanismIn: Annual Review of Genetics Vol. 38 (2004) pp. 709 - 724Online Full Text: dx.doi.org/
-
Crystal structure of DegP (HtrA) reveals a new protease-chaperone machineIn: Nature Vol. 416 (2002) Nr. 6879, pp. 455 - 459
-
The HtrA family of proteases : Implications for protein composition and cell fateIn: Molecular Cell Vol. 10 (2002) Nr. 3, pp. 443 - 455Online Full Text: dx.doi.org/