Research

My research group is interested in chaperone-protease complexes. These molecular degradation machines, responsible for the breakdown of a large variety of protein substrates, play an important role in regulation and quality control mechanisms inside cells. They are composed of a proteolytic core cylinder and a donut-shaped chaperone complex, binding to either end of the core cylinder. The chaperone rings act as “entry-guards” and represent the sites of substrate recognition and preparation. I am interested in the mechanism of action of these machines on the molecular level.
Model systems we are using for our studies are the bacterial ClpAP chaperone-protease assembly and the archaeal PAN-proteasome complex.

Recently we have focussed our attention on a proteasome-system found in certain bacteria, amongst them the highly pathogenic Mycobacterium tuberculosis. In this organism, the proteasome and its ATPase partner Mpa contribute to pathogenicity by supporting the persistence in the lung macrophages. Substrates are recruited by a ubiquitin-like pathway termed pupylation, wherein the small protein Pup (prokaryotic ubiquitin-like protein) is conjugated to lysine residues of protein substrates.