In the early life of a protein, proper folding is the prerequisite to perform its dedicated function. At the end of the road, a protein’s fate is degradation, typcially preceded by dissociation of oligomeric complexes and unfolding of the polypeptide chain. The goal of our research is to understand the cellular machinery that mediates these intricate processes. Successful protein folding requires the assistance of molecular chaperones. Members of this diverse group of proteins can prevent aggregation and promote folding of their protegés to the native state. Of particular interest for us are cylindrical chaperonins, which enclose folding proteins within their interior cavity. We investigate and compare the molecular properties of bacterial and archaeal chaperonins, using a variety of biochemical and biophysical techniques.
Unfolding of proteins is achieved by ring-shaped AAA ATPases, which channel their substrates to large proteases like the proteasome for subsequent degradation. We are interested in the interplay of prokaryotic AAA ATPases with their substrates, with chaperones and with proteases, and would like to find out how ATP hydrolysis is mechanistically coupled to protein unfolding.
A hallmark of protein degradation in eukaryotes is tagging of candidate substrates with poly-ubiquitin chains. In prokaryotes, much less is known about the selection of proteins for unfolding and degradation. It appears, however, that conjugation with small marker proteins is a universally used principle. Expanding on recent findings, we aim to understand how different protein conjugation systems in bacteria and archaea evolved.