Post-translational modifications near the quinone binding site of mammalian complex I.

TitlePost-translational modifications near the quinone binding site of mammalian complex I.
Publication TypeJournal Article
Year of Publication2013
AuthorsCarroll, J, Ding, S, Fearnley, IM, Walker, JE
JournalJ Biol Chem
Date Published2013 Aug 23
KeywordsAnimals, Bacterial Proteins, Binding Sites, Cattle, Electron Transport Complex I, Flavin Mononucleotide, Fungal Proteins, HEK293 Cells, Humans, Lipid Bilayers, Mitochondria, Heart, NAD, Paracoccus denitrificans, Pichia, Structural Homology, Protein, Thermus thermophilus, Ubiquinone

Complex I (NADH:ubiquinone oxidoreductase) in mammalian mitochondria is an L-shaped assembly of 44 protein subunits with one arm buried in the inner membrane of the mitochondrion and the orthogonal arm protruding about 100 Å into the matrix. The protruding arm contains the binding sites for NADH, the primary acceptor of electrons flavin mononucleotide (FMN), and a chain of seven iron-sulfur clusters that carries the electrons one at a time from FMN to a coenzyme Q molecule bound in the vicinity of the junction between the two arms. In the structure of the closely related bacterial enzyme from Thermus thermophilus, the quinone is thought to bind in a tunnel that spans the interface between the two arms, with the quinone head group close to the terminal iron-sulfur cluster, N2. The tail of the bound quinone is thought to extend from the tunnel into the lipid bilayer. In the mammalian enzyme, it is likely that this tunnel involves three of the subunits of the complex, ND1, PSST, and the 49-kDa subunit. An arginine residue in the 49-kDa subunit is symmetrically dimethylated on the ω-N(G) and ω-N(G') nitrogen atoms of the guanidino group and is likely to be close to cluster N2 and to influence its properties. Another arginine residue in the PSST subunit is hydroxylated and probably lies near to the quinone. Both modifications are conserved in mammalian enzymes, and the former is additionally conserved in Pichia pastoris and Paracoccus denitrificans, suggesting that they are functionally significant.

Alternate JournalJ. Biol. Chem.
Citation Key10.1074/jbc.M113.488106
PubMed ID23836892
PubMed Central IDPMC3750175
Grant ListMC_U105663148 / / Medical Research Council / United Kingdom