Research Interest

Ubiquitin-proteasome System

Currently, the main project areas within the team concern the structure of the 26S proteasome (shown in the figure) and the COP9 signalosome, both of which play central roles in the ubiquitin proteasome system. 

Selective protein removal is an essential regulatory mechanism in cellular homeostasis and cell division. The ubiquitin-proteasome system is responsible for the highly regulated targeting and proteolysis of such proteins. 

Within the ubiquitin-proteasome pathway:

• The COP9 signalosome acts to regulate, by deneddylation, a class of E3 ligases, which covalently attach ubiquitin to proteins targeted for degradation. 
• The 26S proteasome is a very large multi-subunit protease responsible for the recognition, unfolding and degradation of substrates which have been labelled by ubiquitin. 

The full knowledge of the structural and functional organisation and of such complexes is a prerequisite for the full understanding of their regulatory roles in the cell allowing for more specific targeting of the relevant pathways.

Structure of the 26S proteasome determined by cryo-electron microscopy and single particle analysis at a resolution of  ~ 8 Angstroms. 
Semitransparent surface representations corresponding to views parallel to and orthogonal from the molecular twofold axis are shown. The structure consists of a 20S core particle and two 19S regulatory particles. Docked models for the 20S core and the Rpt1-6 subunits of the 19S regulatory particles are shown as colour-coded cartoons.