Structural Bioenergetics Group
Head: Prof. Volker Zickermann
Proton pumping NADH:ubiquinone oxidoreductase (complex I) is a very large membrane protein complex with a key function for efficient energy production of the cell. The minimal form of complex I found in bacteria comprises 14 conserved subunits. The larger and more complicated enzyme of the mitochondrial respiratory chain harbors more than 40 subunits with a total mass of almost 1 MDa.
Complex I utilizes the redox energy released in the electron transfer reaction from NADH to ubiquinone to pump protons across the inner mitochondrial membrane or the cell membrane of bacteria. Redox linked proton transloaction by complex I contributes significantly to the electrochemical proton gradient that ultimately drives ATP synthesis in oxidative phosphorylation. A variety of neuromuscular and neurodegenerative human diseases has been linked with complex I dysfunction. However, the molecular details of energy conversion by complex I are still poorly understood. We use the aerobic yeast Yarrowia lipolytica as a yeast genetic model system to study eukaryotic complex I. Protein purification by His-tag affinity purification and genetic manipulation of nuclear encoded subunits is straightforward. We have accomplished the first X-ray crystallographic analysis of mitochondrial complex I. The structure provided exciting insight into the molecular basis of redox-driven proton pumping. Our work is supported by the Deutsche Forschungsgemeinschaft (ZI 552/3-1, ZI 552 4-1 and EXC 115);and our goal is to obtain a comprehensive understanding of complex I, a giant molecular machine.