Assemblierung des Atmungsketten Komplex I

The proton-pumping NADH:ubiquinone oxidoreductase, also called complex I, is the first of the respiratory complexes providing the proton motive force which is essential for the synthesis of ATP. We try to understand the assembly, structure and function of this enzyme using the fungus Neurospora crassa as model organism. Our current research basically follows two lines.
A major goal of our studies is to understand the processes linking electron and proton translocation. While the epr detectable iron-sulfur clusters and the FMN which are prosthetic groups of the matrix arm of complex I are rather well characterized, very little is known about redox reactions taking place in the membrane arm. Employing time resolved UV/VIS-spectroscopy we try to gain access to so far uncharacterized redox groups. The biggest challenge posed by complex I is the elucidation of its high resolution structure. All efforts to clarify the enzymatic mechanism of complex I are futile without knowledge of the detailed three-dimensional structure. To this end we crystallize complex I and its subcomplexes for x-ray analysis.
The second focus is the identification of proteins involved in the assembly of the complex. Two subunits of complex I, one functioning as acyl carrier protein and the other being a NADPH-dependent reductase/isomerase, appear to have biosynthetic functions. Two other proteins, designated CIA proteins, have been characterized which are associated transiently with an assembly intermediate of complex I and might be complex I specific chaperone type proteins.