Quinone binding and reduction by respiratory complex I.
Complex I (NADH:ubiquinone oxidoreductase) has a central function in oxidative phosphorylation and hence for efficient ATP production in most prokaryotic and eukaryotic cells. This huge membrane protein complex transfers electrons from NADH to ubiquinone and couples this exergonic redox reaction to endergonic proton pumping across bioenergetic membranes. Although quinone reduction seems to be critical for energy conversion, this part of the reaction is least understood. Here we summarize and discuss experimental evidence indicating that complex I contains an extended ubiquinone binding pocket at the interface of the 49-kDa and PSST subunits. Close to iron-sulfur cluster N2, the proposed immediate electron donor for ubiquinone, a highly conserved tyrosine constitutes a critical element of the quinone reduction site. A possible quinone exchange path leads from cluster N2 to the N-terminal β-sheet of the 49-kDa subunit. We discuss the possible functions of a highly conserved HRGXE motif and a redox-Bohr group associated with cluster N2. Resistance patterns observed with a large number of point mutations suggest that all types of hydrophobic complex I inhibitors also act at the interface of the 49-kDa and the PSST subunit. Finally, current controversies regarding the number of ubiquinone binding sites and the position of the site of ubiquinone reduction are discussed.
Tocilescu
Maja A
MA
Molecular Bioenergetics Group, Medical School, Cluster of Excellence Frankfurt "Macromolecular Complexes," Center for Membrane Proteomics, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany. Mat2174@Columbia.edu
Zickermann
Volker
V
Zwicker
Klaus
K
Brandt
Ulrich
U
D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016227:Benzoquinones / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D042967:Electron Transport Complex I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D009154:Mutation; D010084:Oxidation-Reduction; D011485:Protein Binding; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016963:Thermus thermophilus / Q000201:enzymology*
D001426:Bacterial Proteins; D016227:Benzoquinones; D021122:Protein Subunits; C004532:quinone; D042967:Electron Transport Complex I