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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....
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2014
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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. |
format | Online Article Text |
id | pubmed-4224586 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT vinothkumarkuttir architectureofmammalianrespiratorycomplexi AT zhujiapeng architectureofmammalianrespiratorycomplexi AT hirstjudy architectureofmammalianrespiratorycomplexi |