title: A possible role for iron-sulfur cluster N2 in proton translocation by the NADH: ubiquinone oxidoreductase (complex I).
abstract: The proton-pumping NADH:ubiquinone oxidoreductase, the respiratory complex I, couples the transfer of electrons from NADH to ubiquinone with the translocation of protons across the membrane. The enzyme mechanism is still unknown due to the lack of a high-resolution structure and its complicated composition. The complex from Escherichia coli is made up of 13 subunits called NuoA through NuoN and contains one FMN and nine iron-sulfur (Fe/S) clusters as redox groups. The pH dependence of the midpoint redox potential of the Fe/S cluster named N2 and its spin-spin interaction with ubiquinone radicals made it an ideal candidate for a key component in redox-driven proton translocation. During the past years we have assigned the subunit localization of cluster N2 to subunit NuoB by site-directed mutagenesis and predicted its ligation by molecular simulation. Redox-induced FT-IR spectroscopy has shown that its redox reaction is accompanied by the protonation and deprotonation of individual amino acid residues. These residues have been identified by site-directed mutagenesis. The enzyme catalytic activity depends on the presence of cluster N2 and is coupled with major conformational changes. From these data a model for redox-induced conformation-driven proton translocation has been derived.
authors.affiliation: Institut für Organische Chemie und Biochemie, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Flemming
authors.forename: Stefan
authors.initials: S
authors.lastname: Stolpe
authors.forename: Daniel
authors.initials: D
authors.lastname: Schneider
authors.forename: Petra
authors.initials: P
authors.lastname: Hellwig
authors.forename: Thorsten
authors.initials: T
authors.lastname: Friedrich
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D004579:Electron Transport; D042967:Electron Transport Complex I / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D011522:Protons; D017386:Sequence Homology, Amino Acid; D013455:Sulfur / Q000378:metabolism; D014451:Ubiquinone / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D007506:Iron-Sulfur Proteins; D021122:Protein Subunits; D011522:Protons; D014451:Ubiquinone; D013455:Sulfur; D007501:Iron; D042967:Electron Transport Complex I