We want to solve the structure and study the function of Tom40, the central protein of the large integral membrane protein complex Tom by using advanced solution NMR techniques. These studies are the first step on the way to characterize the full Tom complex and its inter­actions at atomic resolution, which we pursue as a longer range goal. The eukaryotic integral membrane protein complex Tom is the pore in the outer membrane of mitochondria responsible for protein import. Based on the structural studies of Tom40, its interactions with the other Tom-proteins (receptors Tom20 and Tom70; auxiliary proteins Tom5, Tom6 and Tom22) and additional interaction partners within the whole complex will become possible. Especially for yeast (S. cerevisiae) and the fungus N. crassa a lot of biochemical data is available, the interpretation of which would highly benefit from an atomic resolution structure. This structural information would directly lead to a more detailed understanding of the mitochondrial import mechanism. NMR spectroscopy has emerged as a method of choice to analyze the structure and dynamics of molecular complexes in atomic detail. Improved NMR techniques like TROSY-type experiments along with improved isotope-labeling schemes reduce the effect of fast transverse relaxation for large proteins, and have thus enabled the characterization of large protein com­plexes with a size of several hundred kDa by NMR in recent years. In the present proposal, we want to apply and further develop these methods to characterize the TOM membrane protein complex. Besides answers to our biological objectives, we anticipate technical improvements of solution NMR techniques from our work, which will be of great value for studies on other integral membrane proteins.