Lorenz, Sonja, Dr.
Independent Group Leader
- 2003 Diploma in Biochemistry, University of Regensburg, Germany
- 2004 - 2008 Ph.D. Student, Laboratories of Iain D. Campbell & Martin Noble, University of Oxford, United Kingdom
- 2009 - 2013 Leukemia & Lymphoma Society, Career Development Fellow, Laboratory of John Kuriyan, University of California, Berkeley, CA, USA
- 2013-2014 Howard Hughes Medical Institute, Research Associate, Laboratory of John Kuriyan, University of California, Berkeley, CA, USA
- 2014-2020 Emmy Noether Group Leader, Rudolf Virchow Center for Experimental Biomedicine, University of Wuerzburg, Germany
- Since 2021 Independent Group Leader, MPI for Biophysical Chemistry, Goettingen, Germany
Major Research Interests
1. Catalysis, specificity, and conformational dynamics of the ubiquitination machinery
2. Function of ubiquitin ligases in neurodevelopmental and infectious diseases
3. Therapeutic exploitation of ubiquitination enzymes
Ubiquitination is a central posttranslational modification that dynamically decorates ~50.000 cellular protein sites with specific ubiquitin chains, thereby regulating virtually all aspects of eukaryotic physiology. The ubiquitin system is thus of immense interest to fundamental research and has emerged as a major arena for drug discovery. Our lab aims to establish structural paradigms of specificity in this fascinating system. In particular, we identify, reconstitute, and structurally characterize macromolecular complexes of ubiquitination enzymes to reveal how these assemblies encode substrate and linkage specificity in ubiquitin chain formation. Our group combines the entire spectrum of high-resolution structural techniques (cryo-electron microscopy, X-ray crystallography, and NMR) with chemical biology-based crosslinking, biophysical, and cell biological techniques. We utilize our structural insights for the development of small-molecule probes targeting critical protein interfaces. Such compounds provide useful tools to interrogate ubiquitination activities in the cell and proof-of-principle precursors for future therapeutic applications.
Ongoing lines of research focus on yet uncharacterized HECT-type ubiquitin ligases with important roles in neurodevelopmental and infectious diseases.
Homepage Department/Research Group
Selected Recent Publications
- Liess A*, Kucerova A*, Schweimer K, Urlaub H, Mansfeld J#, and Lorenz S#
Dimerization regulates the human APC/C-associated ubiquitin-conjugating enzyme UBE2S.
Science Signal. 2020; 13: eaba8208
- Liess A*, Kucerova A*, Schweimer K, Yu L, Roumeliotis T, Diebold M, Dybkov O, Sotriffer C, Urlaub H, Choudhary J, Mansfeld J#, and Lorenz S#
Mechanism of auto-inhibition of the ubiquitin-conjugating enzyme UBE2S by auto-ubiquitination.
Structure. 2019; 27: 1195-1210
- Lee H-J, Li C-F, Ruan D, He J, Montal E D, Lorenz S, Girnun G D, Chang C-H
Non-proteolytic ubiquitination of Hexokinase 2 by HectH9 controls tumorigenesis, energy metabolism and ROS inhibited cancer stem cell expansion.
Nature Comm. 2019; 10: 2625
- Ries L, Deol K, Sander B, Letzelter M-A, Strieter E, Lorenz S
Studies of ubiquitin recognition by the HECT ligase E6AP provide insight into its linkage specificity.
J Biol Chem. 2019; 94: 6113-6129
- Chen D, Gehringer M, Lorenz S
Developing Small-Molecule Inhibitors of HECT-Type Ubiquitin Ligases for Therapeutic Applications: Challenges and Opportunities.
ChemBioChem. 2018; 19: 2123-2135
- Sander B, Xu W, Eilers M, Popov N, Lorenz S
A conformational switch regulates the ubiquitin ligase HUWE1.
eLife. 2017; 6: e21036
- Wickliffe KE*, Lorenz S*#, Wemmer D, Kuriyan J, Rape M#
The mechanism of linkage-specific ubiquitin chain elongation by a single-subunit E2.
Cell. 2011; 144: 769-781
* co-first author
# co-corresponding author