A research topic within the field of molecular biophysics is the structure-function relationship of proteins. Membrane proteins are a large, diverse group of biological macromolecules that perform many different and essential functions for the cell. Despite the abundance and importance of membrane proteins, high-resolution 3D structures from this class of proteins are underrepresented among all yet determined structures. The limited amount of data for membrane proteins hints about the higher difficulty associated with studies of this group of molecules. The determination of an atomic resolution structure is often a long process in which several obstacles need to be overcome, in particular for membrane proteins.

Solution-state nuclear magnetic resonance (NMR) is a powerful measurement technique that can provide high-resolution data on the structure and dynamics of biological macromolecules, and is suitable for studies of small, dynamic membrane proteins. However, even with solution-state NMR, the membrane proteins need to be investigated in environments that are sometimes severely compromising for the protein’s native structure and function. In order to evaluate the biological significance of results obtained under such artificial conditions, supporting data from experiments in more realistic membrane models, obtained using NMR and other biophysical methods, is of great importance.

The work presented in this thesis concerns studies of four membrane proteins: WaaG, Rcf1, Rcf2 and TatA. These proteins have very different characteristics in terms of their sizes and expected membrane interactions, and were accordingly found to be differently affected by the model membranes in which they were studied. Our results illustrate both the current possibilities and limitations of solution-state NMR for studying membrane proteins, and highlight the benefits of an approach where several membrane mimicking systems and measurements techniques are used in combination to arrive at correct conclusions on the properties of proteins.