title: Structure-function relationships in mitochondrial complex I of the strictly aerobic yeast Yarrowia lipolytica.
abstract: The obligate aerobic yeast Yarrowia lipolytica has been established as a powerful model system for the analysis of mitochondrial complex I. Using a combination of genomic and proteomic approaches, a total of 37 subunits was identified. Several of the accessory subunits are predicted to be STMD (single transmembrane domain) proteins. Site-directed mutagenesis of Y. lipolytica complex I has provided strong evidence that a significant part of the ubiquinone reducing catalytic core resides in the 49 kDa and PSST subunits and can be modelled using X-ray structures of distantly related enzymes, i.e. water-soluble [NiFe] hydrogenases from Desulfovibrio spp. Iron-sulphur cluster N2, which is related to the hydrogenase proximal cluster, is directly involved in quinone reduction. Mutagenesis of His226 and Arg141 of the 49 kDa subunit provided detailed insight into the structure-function relationships around cluster N2. Overall, our findings suggest that proton pumping by complex I employs long-range conformational interactions and ubiquinone intermediates play a critical role in this mechanism.
authors.affiliation: Universität Frankfurt, Zentrum der Biologischen Chemie, Molekulare Bioenergetik, Theodor-Stern-Kai 7, Haus 26, D-60590 Frankfurt am Main, Germany. brandt@zbc.kgu.de
authors.forename: U
authors.initials: U
authors.lastname: Brandt
authors.forename: A
authors.initials: A
authors.lastname: Abdrakhmanova
authors.forename: V
authors.initials: V
authors.lastname: Zickermann
authors.forename: A
authors.initials: A
authors.lastname: Galkin
authors.forename: S
authors.initials: S
authors.lastname: Dröse
authors.forename: K
authors.initials: K
authors.lastname: Zwicker
authors.forename: S
authors.initials: S
authors.lastname: Kerscher
mesh_terms: D000332:Aerobiosis; D042967:Electron Transport Complex I / Q000737:chemistry / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D005658:Fungi / Q000201:enzymology; D008928:Mitochondria / Q000201:enzymology*; D008958:Models, Molecular; D008970:Molecular Weight; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D025062:Yarrowia / Q000201:enzymology*; D015003:Yeasts / Q000201:enzymology
chemical_list: D005656:Fungal Proteins; D011994:Recombinant Proteins; D042967:Electron Transport Complex I