ZMB Member Michael Ehrmann

Michael Ehrmann

Prof. Dr. Michael Ehrmann

Phone: +49 201 183 2949
Email

Fakultät für Biologie
Microbiology
Room S03 S02 A40
Universität Duisburg-Essen
45117 Essen

Website Group Ehrmann:

Ehrmann Lab - Microbiology

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.

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    Journal articles

  • Merdanovic, Melisa; Burston, Steven G.; Schmitz, Anna Laura; Köcher, Steffen; Knapp, Stefan; Clausen, Tim; Kaiser, Markus; Huber, Robert; Ehrmann, Michael
    Activation by substoichiometric inhibition
    In: Proceedings of the National Academy of Sciences of the United States of America Vol. 117 (2020) Nr. 3, pp. 1414 - 1418
    ISSN: 1091-6490; 0027-8424
  • Köcher, Steffen; Resch, Sarah; Kessenbrock, Till; Schrapp, Lukas; Ehrmann, Michael; Kaiser, Markus
    From dolastatin 13 to cyanopeptolins, micropeptins, and lyngbyastatins : the chemical biology of Ahp-cyclodepsipeptides
    In: Natural Product Reports Vol. 37 (2020) Nr. 2, pp. 163 - 174
    ISSN: 0265-0568; 1460-4752
  • Weil, Tatjana; Groß, Rüdiger; Röcker, Annika; Bravo-Rodriguez, Kenny; Heid, Christian; Sowislok, Andrea; Le, My-Hue; Erwin, Nelli; Dwivedi, Mridula; Bart, Stephen M.; Bates, Paul; Wettstein, Lukas; Müller, Janis A.; Harms, Mirja; Sparrer, Konstantin; Ruiz-Blanco, Yasser B.; Stürzel, Christina M.; von Einem, Jens; Lippold, Sina; Read, Clarissa; Walther, Paul; Hebel, Marco; Kreppel, Florian; Klärner, Frank-Gerrit; Bitan, Gal; Ehrmann, Michael; Weil, Tanja; Winter, Roland; Schrader, Thomas; Shorter, James; Sanchez-Garcia, Elsa; Münch, Jan
    Supramolecular Mechanism of Viral Envelope Disruption by Molecular Tweezers
    In: Journal of the American Chemical Society Vol. 142 (2020) Nr. 40, pp. 17024 - 17038
    ISSN: 1520-5126; 0002-7863
  • Körver, Lisa; Papadopoulos, Chrisovalantis; Liu, Bin; Kravic, Bojana; Rota, Giulia; Brecht, Lukas; Veenendaal, Tineke; Polajnar, Mira; Blümke, Anika; Ehrmann, Michael; Klumperman, Judith; Jäättelä, Marja; Behrends, Christian; Meyer, Hemmo
    The ubiquitin-conjugating enzyme UBE2QL1 coordinates lysophagy in response to endolysosomal damage
    In: EMBO Reports (2019) pp. e48014
    ISSN: 1469-3178; 1469-221X
  • Köcher, Steffen; Rey, Juliana; Bongard, Jens; Tiaden, André N.; Meltzer, Michael; Richards, Peter J.; Ehrmann, Michael; Kaiser, Markus
    Tailored Ahp-cyclodepsipeptides as Potent Non-covalent Serine Protease Inhibitors
    In: Angewandte Chemie International Edition Vol. 56 (2017) Nr. 29, Special Issue: 100th Anniversary of the Royal Australian Chemical Institute, pp. 8555 - 8558
    ISSN: 1521-3773; 1433-7851
  • Sprengel, Andreas; Lill, Pascal; Stegemann, Pierre; Bravo-Rodriguez, Kenny; Schöneweiß, Elisa-Charlott; Merdanovic, Melisa; Gudnason, Daniel; Aznauryan, Mikayel; Gamrad; Barcikowski, Stephan; Sanchez-Garcia, Elsa; Birkedal, Victoria; Gatsogiannis, Christos; Ehrmann, Michael; Sacca, Barbara
    Tailored protein encapsulation into a DNA host using geometrically organized supramolecular interactions
    In: Nature Communications Vol. 8 (2017) pp. 14472
    ISSN: 2041-1723
  • Poepsel, Simon; Sprengel, Andreas; Sacca, Barbara; Kaschani, Farnusch; Kaiser, Markus; Gatsogiannis, Christos; Raunser, Stefan; Clausen, Tim; Ehrmann, Michael
    Determinants of amyloid fibril degradation by the PDZ protease HTRA1
    In: Nature Chemical Biology Vol. 11 (2015) Nr. 11, pp. 862 - 869
    ISSN: 1552-4450; 1552-4469
  • Beaufort, Nathalie; Scharrer, Eva; Lux, Vanda; Ehrmann, Michael; Haffner, Christof; Dichgans, Martin
    Reply to Liu et al. : Loss of TGF-β signaling in CARASIL pathogenesis
    In: Proceedings of the National Academy of Sciences of the United States of America Vol. 112 (2015) Nr. 14, pp. E1694
    ISSN: 1091-6490; 0027-8424
  • Beaufort, Nathalie; Scharrer, Eva; Kremmer, Elisabeth; Lux, Vanda; Ehrmann, Michael; Huber, Robert; Houlden, Henry H.; Werring, David John; Haffner, Christof; Dichgans, Martin
    Cerebral small vessel disease-related protease HtrA1 processes latent TGF-β binding protein 1 and facilitates TGF-β signaling
    In: Proceedings of the National Academy of Sciences of the United States of America Vol. 111 (2014) Nr. 46, pp. 16496 - 16501
    ISSN: 1091-6490; 0027-8424
  • Malet, Hélène; Canellas, Flavia; Sawa, Justyna; Yan, Jun; Thalassinos, Konstantinos; Ehrmann, Michael; Clausen, Tim; Saibil, Helen R.
    Newly folded substrates inside the molecular cage of the HtrA chaperone DegQ
    In: Nature Structural & Molecular Biology Vol. 19 (2012) Nr. 2, pp. 152 - 157
    ISSN: 1545-9993
  • Clausen, Tim; Kaiser, Markus; Huber, Robert; Ehrmann, Michael
    HTRA proteases : regulated proteolysis in protein quality control
    In: Nature Reviews Molecular Cell Biology Vol. 12 (2011) Nr. 3, pp. 152 - 162
    ISSN: 1471-0072
  • Sinha, Sharmistha; Lopes, Dahabada H. J.; Du, Zhenming; Pang, Eric S.; Shanmugam, Akila; Lomakin, Aleksey; Talbiersky, Peter; Tennstaedt, Annette; McDaniel, Kirsten; Bakshi, Reena; Kuo, Pei-Yi; Ehrmann, Michael; Benedek, George B.; Loo, Joseph A.; Klärner, Frank-Gerrit; Schrader, Thomas; Wang, Chunyu; Bitan, Gal
    Lysine-specific molecular tweezers are broad-spectrum inhibitors of assembly and toxicity of amyloid proteins
    In: Journal of the American Chemical Society Vol. 133 (2011) Nr. 42, pp. 16958 - 16969
    ISSN: 0002-7863; 1520-5126
  • Wu, Junchen; Zawistowski, Adam; Ehrmann, Michael; Yi, Tao; Schmuck, Carsten
    Peptide Functionalized Polydiacetylene Liposomes Act as a Fluorescent Turn-On Sensor for Bacterial Lipopolysaccharide
    In: Journal of the American Chemical Society Vol. 133 (2011) Nr. 25, pp. 9720 - 9723
    ISSN: 0002-7863; 1520-5126
  • Merdanovic, Melisa; Clausen, Tim; Kaiser, Markus; Huber, Robert; Ehrmann, Michael
    Protein quality control in the bacterial periplasm
    In: Annual Review of Microbiology Vol. 65 (2011) pp. 149 - 168
    ISSN: 1545-3251; 0066-4227
  • Kley, Juliane; Schmidt, Bastian; Boyanov, Boril; Stolt-Bergner, Peggy C.; Kirk, Rebecca; Ehrmann, Michael; Knopf, Ronit R.; Naveh, Leah; Adam, Zach; Clausen, Tim
    Structural adaptation of the plant protease Deg1 to repair photosystem II during light exposure
    In: Nature Structural & Molecular Biology Vol. 18 (2011) Nr. 6, pp. 728 - 731
    ISSN: 1545-9993
  • Trübestein, Linda; Tennstaedt, Annette; Mönig, Timon; Krojer, Tobias; Canellas, Flavia; Kaiser, Markus; Clausen, Tim; Ehrmann, Michael
    Substrate induced remodeling of the active site regulates human HtrA1 activity
    In: Nature Structural & Molecular Biology Vol. 18 (2011) pp. 386 - 388
    ISSN: 1545-9993
  • Merdanovic, Melisa; Mamant, Nicolette; Meltzer, Michael; Poepsel, Simon; Auckenthaler, Alexandra; Melgaard, Rie; Hauske, Patrick; Nagel-Steger, Luitgard; Clarke, Anthony R.; Kaiser, Markus; Huber, Robert; Ehrmann, Michael
    Determinants of structural and functional plasticity of a widely conserved protease chaperone complex
    In: Nature Structural & Molecular Biology Vol. 17 (2010) Nr. 7, pp. 837 - 843
    ISSN: 1545-9993; 1545-9985
  • Meltzer, Michael; Hasenbein, Sonja; Hauske, Patrick; Kucz, Nicolette; Merdanovic, Melisa; Grau, Sandra; Beil, Alexandra; Jones, Dafydd; Krojer, Tobias; Clausen, Tim; Ehrmann, Michael; Kaiser, Markus
    Allosteric activation of HtrA protease DegP by stress signals during bacterial protein quality control
    In: Angewandte Chemie International Edition Vol. 47 (2008) Nr. 7, pp. 1332 - 1334
    ISSN: 0044-8249; 0932-2140
  • Krojer, Tobias; Pangerl, Karen; Kurt, Juliane; Sawa, Justyna; Stingl, Christoph; Mechtler, Karl; Huber, Robert; Ehrmann, Michael; Clausen, Tim
    Interplay of PDZ and protease domain of DegP ensures efficient elimination of misfolded proteins
    In: Proceedings of the National Academy of Sciences of the United States of America Vol. 22 (2008) pp. 7702 - 7707
    ISSN: 1091-6490; 0027-8424
  • Krojer, Tobias; Sawa, Justyna; Schäfer, Eva; Saibil, Helen R.; Ehrmann, Michael; Clausen, Tim
    Structural basis for the regulated protease and chaperone function of DegP.
    In: Nature (2008) Nr. 453, pp. 885 - 890
    ISSN: 0028-0836; 1476-4687
  • Hasenbein, Sonja; Merdanovic, Melisa; Ehrmann, Michael
    Determinants of regulated proteolysis in signal transduction
    In: Genes and Development Vol. 21 (2007) Nr. 1, pp. 6 - 10
    ISSN: 0890-9369
  • Hasselblatt, Hanna; Kurzbauer, Robert; Wilken, Corinna; Krojer, Tobias; Sawa, Justyna; Kurt, Juliane; Kirk, Rebecca; Hasenbein, Sonja; Ehrmann, Michael; Clausen, Tim
    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 stress
    In: Genes and Development Vol. 21 (2007) Nr. 20, pp. 2659 - 2670
    ISSN: 0890-9369; 1549-5477
  • Grau, Sandra; Baldi, Alfonso; Bussani, Rossana; Tian, Xiaodan; Stefanescu, Raluca; Przybylski, Michael; Richards, Peter; Jones, Simon A.; Shridhar, Viji; Clausen, Tim; Ehrmann, Michael
    Implications of human HtrA1 in amyloid precursor protein processing.
    In: Proceedings of the National Academy of Sciences of the United States of America Vol. 102 (2005) Nr. 17, pp. 6021 - 6026
    ISSN: 1091-6490; 0027-8424
  • Grau, Sandra; Baldi, Alfonso; Bussani, Rossana; Tian, Xiaodan; Stefanescu, Raluca; Przybylski, Michael; Richards, Peter; Jones, Simon A.; Shridhar, Viji; Clausen, Tim; Ehrmann, Michael
    Implications of the serine protease HtrA1 in amyloid precursor protein processing
    In: Proceedings of the National Academy of Sciences of the United States of America Vol. 102 (2005) Nr. 17, pp. 6021 - 6026
    ISSN: 1091-6490; 0027-8424
  • Henrichs, Tanja; Mikhaleva, Natasha; Conz, Charlotte; Deuerling, Elke; Boyd, Dana; Zelasny, Adrian; Bibi, Eitan; Ban, Nenad; Ehrmann, Michael
    Target-directed proteolysis at the ribosome.
    In: Proceedings of the National Academy of Sciences of the United States of America Vol. 102 (2005) pp. 4246 - 4251
    ISSN: 1091-6490; 0027-8424
  • Wilken, Corinna; Kitzing, Karina; Kurzbauer, Robert; Ehrmann, Michael; Clausen, Tim
    Crystal structure of the DegS stress sensor: How a PDZ domain recognizes misfolded protein and activates a protease
    In: Cell Vol. 117 (2004) Nr. 4, pp. 483 - 494
    ISSN: 0092-8674
  • Ehrmann, Michael; Clausen, Tim
    Proteolysis as a regulatory mechanism
    In: Annual Review of Genetics Vol. 38 (2004) pp. 709 - 724
    ISSN: 0066-4170; 0066-4197
  • Eser, Markus; Ehrmann, Michael
    SecA-dependent quality control of intracellular protein localization
    In: Proceedings of the National Academy of Sciences of the United States of America Vol. 100 (2003) Nr. 23, pp. 13231 - 13234
    ISSN: 1091-6490; 0027-8424
  • Krojer, Tobias; Garrido-Franco, Marta; Hubert, Robert; Ehrmann, Michael; Clausen, Tim
    Crystal structure of DegP (HtrA) reveals a new protease-chaperone machine
    In: Nature Vol. 416 (2002) Nr. 6879, pp. 455 - 459
    ISSN: 0028-0836; 1476-4687
  • Clausen, Tim; Southan, Chris; Ehrmann, Michael
    The HtrA family of proteases: Implications for protein composition and cell fate
    In: Molecular Cell Vol. 10 (2002) Nr. 3, pp. 443 - 455
    ISSN: 1097-2765
  • Herskovits, Anat A.; Seluanov, Andrei; Rajsbaum, Ricardo; ten Hagen-Jongman, Corinne M.; Henrichs, Tanja; Bochkareva, Elena S.; Phillips, Gregory J.; Probst, Francis J.; Nakae, Taiji; Ehrmann, Michael; Luirink, Joen; Bibi, Eitan
    Evidence for coupling of membrane targeting and function of the signal recognition particle (SRP) receptor Fts Y
    In: EMBO Reports Vol. 2 (2001) Nr. 11, pp. 1040 - 1046
    ISSN: 1469-221X
  • Spiess, Christoph; Beil, Alexandra; Ehrmann, Michael
    A temperature-dependent switch from chaperone to protease in a widely conserved heat shock protein
    In: Cell Vol. 97 (1999) Nr. 3, pp. 339 - 347
    ISSN: 0092-8674
  • Ehrmann, Michael; Bolek, Petra; Mondigler, Martin; Boyd, Dana; Lange, Roland
    TnTIN and TnTAP: Mini-transposons for site-specific proteolysis in vivo
    In: Proceedings of the National Academy of Sciences of the United States of America Vol. 94 (1997) Nr. 24, pp. 13111 - 13115
    ISSN: 1091-6490; 0027-8424
  • Ehrmann, Michael; Boyd, Dana; Beckwith, Jonathan
    Genetic analysis of membrane protein topology by a sandwich gene fusion approach.
    In: Proceedings of the National Academy of Sciences of the United States of America Vol. 87 (1990) Nr. 19, pp. 7574 - 7578
    ISSN: 1091-6490; 0027-8424

ZMB Research Programme

Prof. Michael Ehrmann participates in the ZMB research programme III, Molecular and Chemical Cell Biology.

DFG Collaborative Research Centre 1093 Supramolecular Chemistry on Proteins

B1: Supramolecular ligands modulate assembly and function of HtrA proteases

Europäischer Fonds für regionale Entwicklung EFRE Project

Inhibitors of the serin protease HTRA1 for the treatment of age-related blindness (2018-2022)

Participating Institutions
Lead Discovery Center GmbH, Dortmund
University of Duisburg-Essen