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-Structure paper
Title | Architecture of mammalian respiratory complex I. |
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Journal, issue, pages | Nature, Vol. 515, Issue 7525, Page 80-84, Year 2014 |
Publish date | Nov 6, 2014 |
Authors | Kutti R Vinothkumar / Jiapeng Zhu / Judy Hirst / |
PubMed Abstract | Complex I (NADH:ubiquinone oxidoreductase) is essential for oxidative phosphorylation in mammalian mitochondria. It couples electron transfer from NADH to ubiquinone with proton translocation across ...Complex I (NADH:ubiquinone oxidoreductase) is essential for oxidative phosphorylation in mammalian mitochondria. It couples electron transfer from NADH to ubiquinone with proton translocation across the energy-transducing inner membrane, providing electrons for respiration and driving ATP synthesis. Mammalian complex I contains 44 different nuclear- and mitochondrial-encoded subunits, with a combined mass of 1 MDa. The 14 conserved 'core' subunits have been structurally defined in the minimal, bacterial complex, but the structures and arrangement of the 30 'supernumerary' subunits are unknown. Here we describe a 5 Å resolution structure of complex I from Bos taurus heart mitochondria, a close relative of the human enzyme, determined by single-particle electron cryo-microscopy. We present the structures of the mammalian core subunits that contain eight iron-sulphur clusters and 60 transmembrane helices, identify 18 supernumerary transmembrane helices, and assign and model 14 supernumerary subunits. Thus, we considerably advance knowledge of the structure of mammalian complex I and the architecture of its supernumerary ensemble around the core domains. Our structure provides insights into the roles of the supernumerary subunits in regulation, assembly and homeostasis, and a basis for understanding the effects of mutations that cause a diverse range of human diseases. |
External links | Nature / PubMed:25209663 / PubMed Central |
Methods | EM (single particle) |
Resolution | 4.95 Å |
Structure data | |
Chemicals | ChemComp-SF4: ChemComp-FES: |
Source |
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Keywords | OXIDOREDUCTASE / NADH DEHYDROGENASE / RESPIRATORY COMPLEX |