Detergent-protein interactions

The project involves an analysis of the interactions between a comprehensive series of commonly used detergents and two bacterial membrane proteins, namely the inner membrane protein DsbB and the membrane-bound domain of the outer membrane protein OmpA. The overall aim is to obtain further insight in detergent parameters governing membrane protein stability and solubility. We have already established that we can determine the stability and folding of these two proteins with straightforward fluorescence-based methods. In addition to studying the stability of the intact proteins in mixed micelles where SDS is used as a denturant, we will measure the association of the cleaved membrane proteins in pure detergents. We also intend to carry out a detailed characterization of the influence of the membrane proteins on micelle structure, which may lay the groundwork for the determination of the structure of DsbB by NMR. Longer term perspectives include single micelle measurements with external collaborators. We will also draw on our considerable insights into the kinetics of detergent interactions with water-soluble proteins. All in all, the project represents a unique opportunity to obtain accurate and systematic data within a field that is still at an early stage in the understanding of protein-detergent interactions. In addition to basic research aspects, the project is expected to have practical consequences for the purification and general handling of membrane proteins.