Lorenz, Sonja, Prof. Dr.

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

https://www.mpinat.mpg.de/de/lorenz

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