Investigating the essential roles of Ubiquitin-like molecules and the Ubiquitin Proteasome System

David Komander

Education

  • 2005: PhD in Biochemistry from University of Dundee, Scotland.
  • 2002: Diploma in Biochemistry from Ruhr-University Bochum, Germany.

Research Appointments

  • 2008: Group Leader at MRC Laboratory of Molecular Biology, Cambridge, UK.
  • 2006: Beit Memorial Fellow for Medical Research at ICR London, UK.
  • 2005: CRUK Postdoctoral Fellow at The Institute of Cancer Research (ICR) London, UK.
David Komander

Research Interests

We are interested in the specificity of the ubiquitin system, and aim to understand and differentiate the roles of the eight distinct ubiquitin chain types in cells, with a particular emphasis on the unstudied ‘atypical’ ubiquitin linkages. We use a ‘reverse engineering’ approach, starting at the ubiquitin chains themselves. We analyse atypical chains and use them as tools to identify proteins that act on these linkages specificially. These proteins allow us to link atypical ubiquitin chains to the processes they regulate.

Linked diubiquitins

Figure 1. Structures of differently linked diubiquitins Blue surfaces indicate the hydrophobic patch of ubiquitin used in protein recognition.

 

Selected Publications 

Komander, D. and Rape, M. (2012), “The Ubiquitin Code”, Annu Rev Biochem 81:203-29.

Licchesi J.D.F., Mieszczanek J., Mevissen T.E.T., Rutherford T.J., Akutsu M., Virdee S., El Oualid F., Chin J.W., Ovaa H., Bienz M. and Komander D. (2011) “An Ankyrin-repeat ubiquitin binding domain in Trabid determines its specificity for Lys29- and Lys33-linked polyubiquitin”, Nat Struct Mol Biol 19(1): 62-71.

Ye Y., Akutsu M., Reyes-Turcu F., Wilkinson K.D. and Komander D. (2011), “Molecular basis for cross-reactivity in the deubiquitinase USP21”, EMBO Rep  12(4): 350-7.

Akutsu M., Ye Y., Virdee S., Chin J.W. and Komander D. (2011), “Molecular Basis for ubiquitin and ISG15 cross-reactivity in viral OTU domains”, Proc Nat Acad Sci USA 108(6): 2228-33.      

Virdee S., Ye Y., Nguyen D.P., Komander D. and Chin J.W. (2010), “Engineered diubiquitin synthesis reveals Lys29-isopeptide specificity of an OTU deubiquitinase”, Nat Chem Biol 6(10): 750-7.                                                                                                   

Bremm A., Freund S.M. and Komander D. (2010), “Lys11-linked ubiquitin chains adopt compact conformations and are preferentially hydrolyzed by the deubiquitinase Cezanne”, Nat Struct Mol Biol 17(8): 939-47.

Kulathu Y., Akutsu M., Bremm A., Hofmann K. and Komander D. (2009), “Two-sided ubiquitin binding explains specificity of the TAB2 NZF domain”, Nat Struct Mol Biol 16(12): 1328-30.

Komander D., Clague M.J. and Urbé S. (2009), “Breaking the chains: structure and function of the deubiquitinases”, Nat Rev Mol Cell Biol 10(8): 550-63.

Komander D., Reyes-Turcu F., Licchesi J.D., Odenwaelder P., Wilkinson K.D. and Barford D. (2009), “Molecular discrimination of structurally equivalent Lys63-linked and linear polyubiquitin chains”, EMBO Rep 10(5): 466-73.

Rahighi S., Ikeda F., Kawasaki M., Akutsu M., Suzuki N., Kato R., Kensche T., Uejima T., Bloor S., Komander D., Randow F., Wakatsuki S. and Dikic I. (2009) “NEMO binding to linear ubiquitin chains is essential for NF-κB activation”, Cell 136(6): 1098-109.

Partner

MRC

Project

Cellular roles of atypical Ub chains.