The ubiquitin-proteasome system: structural insights into a cellular protein shredder

The attachment of ubiquitin (ubiquitination) to proteins is one of the most abundant protein modifications and targets proteins for degradation. We aim to understand how the ubiquitination reaction works on a structural level, how ubiquitination enzyme activities are regulated, and how ubiquitination regulates cellular processes and behavior. Since dysregulation of ubiquitination is associated with many human diseases, our studies also offer starting points for novel drug design strategies aimed at manipulating ubiquitination enzyme activities with small molecule inhibitors.