Research

Our research activities

focus on the molecular mechanisms by which proteins are translocated across and integrated into cellular membranes. For this purpose, bacteria are outstanding model organisms. They possess an unrivalled diversity of distinct pathways for the export of cytosolically synthesized proteins into one of the layers of the bacterial cell envelope and into the surrounding medium. Furthermore, numerous virulence factors of pathogenic bacteria are secreted by one or the other of those export pathways.

Our central experimental approach

is to reproduce individual protein transport processes in cell-free systems making use of in vitro synthesized substrate proteins and isolated membrane vesicles. A particular objective is to develop and establish highly purified systems that consist of a minimal set of defined components only. To follow the path of a substrate protein across and into the lipid bilayer, we generate transport intermediates that allow identification of their reaction partners by methods such as site-specific cross-linking.

Topics of current research projects

1. Substrate-dependent gating mechanism of the Sec translocon, a protein-conducting channel that has been conserved between all kingdoms of life. Recent structural analyses of the Sec translocon have suggested distinct modes of operation which are awaiting experimental verification.
2. The formation and transport mechanism of the Tat (twin-arginine translocation) translocase. The Tat translocase, which is specific for substrate proteins harbouring a characteristic double-arginine motif in their signal sequences, seems to assemble into an ion-tight channel only upon provision of substrate. A unique and biotechnologically appealing feature is that it can accommodate a large size spectrum of folded substrates.
3. The interplay of molecular chaperones and lipids with the Sec and Tat translocases. Molecular chaperones are involved in targeting translocases as well as in folding newly translocated and membrane-integrated proteins.
4. The type V-secretion pathway of pathogenic bacteria (also called autotransporter and two-partner secretion pathway). Many bacterial virulence factors being secreted by this route possess an N-terminal extension of their signal sequences of unknown function and necessitate coordination of their transport across two membranes.