Ubiquitin-Dependent Cell Signaling

Silke Wiesner

silke wiesner
  • PhD at the EMBL Heidelberg, 1998-03
  • Postdoctoral research at the Hospital for Sick Children,
    University of Toronto, 2003-08
  • Max Planck research group leader at the MPI since 2008

Research Interest

Many proteins function in the cell only at specific subcellular locations and for a limited amount of time. Proteins that are no longer required by the cell get modified with a small protein called Ubiquitin that tags them for degradation. This reaction is catalyzed by the sequential action of an E1, an E2 and a Ubiquitin ligating (E3) enzyme. Ubiquitination represents one of the most common protein modifications in eukaryotes and regulates virtually all signal transduction pathways. Not surprisingly, aberrant ubiquitination enzyme function gives rise to severe cellular dysfunctions that cause numerous human diseases including cancer.

Our lab uses NMR spectroscopy and X-ray crystallography in combination with in vitro and in vivo assays to unravel the molecular mechanism underlying protein ubiquitination and to understand how ubiquitin-modification of proteins regulates cellular processes. In particular, we study the structure, dynamics and interactions of Ubiquitin ligases, as these enzymes are the first in the reaction chain to physically interact with the target protein and thereby directly control the outcome of signal transduction pathways.

  • SWiesner figure1 16
    click to enlarge

Left: Cartoon representation of reaction intermediates formed by HECT-type Ubiquitin ligases. Question marks highlight the unknown mechanisms of Ubiquitin (Ub) transfer from the E2 via the HECT domain to the target protein.

Right: Structural model of the Smurf2 HECT domain (blue) in complex with UbcH7 (E2; green). The catalytic cysteines (yellow) are separated by 47 Å (black line) and thus too remote to provide an explanation for Ubiquitin transfer.

Available PhD Projects

No projects offered in the 2017 selection.

Selected Reading

1) Wiesner S, Ogunjimi AA, Wang HR, Rotin D, Sicheri F, et al. (2007) Autoinhibition of the HECT-type ubiquitin ligase Smurf2 through its C2 domain. Cell 130, 651-62.

2) Stoffregen MC, Schwer MM, Renschler FA, Wiesner S. (2012) Methionine scanning as an NMR tool for detecting and analyzing biomolecular interaction surfaces. Structure 20, 573-81.

3) Mari S, Ruetalo N, Maspero E, Stoffregen MC, Pasqualato S, Polo S, Wiesner S. (2014) Structural and functional framework for the autoinhibition of Nedd4-family ubiquitin ligases. Structure 22, 1639-49.

4) Wiesner S, Sprangers R. (2015) Methyl groups as NMR probes for biomolecular interactions. Curr Opin Struct Biol 35, 60-67.