Structure of mitochondrial complex I and conformational coupling between electron transfer and proton translocation

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Proton pumping NADH:ubiquinone oxidoreductase (mitochondrial complex I) is a very large membrane protein with a key function in energy metabolism. We have accomplished the first X-ray crystallographic analysis of the complete eukaryotic enzyme complex comprising 40 subunits with a mass of almost 1 MDa. Structural information at higher resolution and extended functional characterization will be needed in the future to fully understand its mechanism. We plan to crystallize and determine the structure of stable and functional subcomplexes recently obtained in our laboratory and to use a structure guided fluorescence energy transfer (FRET) approach to investigate functionally critical structural changes during turnover of complex I.