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Architecture of mammalian respiratory complex I

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....

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Autores principales: Vinothkumar, Kutti R., Zhu, Jiapeng, Hirst, Judy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224586/
https://www.ncbi.nlm.nih.gov/pubmed/25209663
http://dx.doi.org/10.1038/nature13686
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author Vinothkumar, Kutti R.
Zhu, Jiapeng
Hirst, Judy
author_facet Vinothkumar, Kutti R.
Zhu, Jiapeng
Hirst, Judy
author_sort Vinothkumar, Kutti R.
collection PubMed
description 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 fourteen 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 significantly 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.
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spelling pubmed-42245862015-05-06 Architecture of mammalian respiratory complex I Vinothkumar, Kutti R. Zhu, Jiapeng Hirst, Judy Nature Article 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 fourteen 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 significantly 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. 2014-09-07 2014-11-06 /pmc/articles/PMC4224586/ /pubmed/25209663 http://dx.doi.org/10.1038/nature13686 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Vinothkumar, Kutti R.
Zhu, Jiapeng
Hirst, Judy
Architecture of mammalian respiratory complex I
title Architecture of mammalian respiratory complex I
title_full Architecture of mammalian respiratory complex I
title_fullStr Architecture of mammalian respiratory complex I
title_full_unstemmed Architecture of mammalian respiratory complex I
title_short Architecture of mammalian respiratory complex I
title_sort architecture of mammalian respiratory complex i
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224586/
https://www.ncbi.nlm.nih.gov/pubmed/25209663
http://dx.doi.org/10.1038/nature13686
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