Folding, stabilization and activity of transmembrane proteins
Membrane proteins are the targets of more than 50% of all drugs in use today. Representing the “gates” for substrates and for (potential) drugs into living cells, membrane proteins are a highly important class of proteins, which is, however, still poorly understood. Our primary goal is to identify and to understand the forces guiding correct folding and stabilization of membrane proteins, prerequisites for a membrane proteins´ activity. We aim to identify contributions of individual amino acids, of protein domains and/or of protein-protein interactions for protein folding and stabilization. Furthermore, it became more and more evident in recent years that the membrane environment itself can control the structure, stability and activity of membrane proteins. In the past, we have already identified contributions of individual membrane lipids and of global membrane properties for the structure and activity of selected membrane integral proteins. In our present chemical-biology approach, we try to identify molecules that allow a directed modulation of membrane properties and, consequently, of the activity of membrane-integrated proteins. Current projects involve analyzes of an ABC-transporter, an aquaglyceroporin as well as of a membrane “organizing” claudine and a fatty acid transporter.
Thylakoid membrane biogenesis in cyanobacteria
How internal membrane systems develop in eukaryotic cells is an active field of current research. In many cases, protein factors mediating membrane biogenesis are identified and their mode of action is described to some extent. However, in contrast to other internal membrane systems, the biogenesis of thylakoid membranes, the internal membrane system in chloroplasts, is poorly understood. Chloroplasts have evolved from a cyanobacterial ancestor, and cyanobacteria are used as (easier to handle) models for chloroplasts. As in chloroplasts, but in contrast to most other bacteria, cyanobacteria also contain two types of internal membrane systems: thylakoid membranes and cytoplasmic membranes. The thylakoid membranes are the place where the photosynthetic light reaction takes place. We are interested in the structure and activity of proteins involved in membrane biogenesis in cyanobacteria (and chloroplasts).
Current projects involve the investigations of the inner membrane associated protein of 30 kDa (IM30) which was demonstrated to mediate membrane fusion, as well as of dynamin-like proteins (DLPs), which are involved in several membrane remodeling processes. Both types of proteins are likely involved in thylakoid membrane biogenesis.