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Structure of the human respiratory complex II
Human complex II is a key protein complex that links two essential energy-producing processes: the tricarboxylic acid cycle and oxidative phosphorylation. Deficiencies due to mutagenesis have been shown to cause mitochondrial disease and some types of cancers. However, the structure of this complex...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10161127/ https://www.ncbi.nlm.nih.gov/pubmed/37098072 http://dx.doi.org/10.1073/pnas.2216713120 |
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author | Du, Zhanqiang Zhou, Xiaoting Lai, Yuezheng Xu, Jinxu Zhang, Yuying Zhou, Shan Feng, Ziyan Yu, Long Tang, Yanting Wang, Weiwei Yu, Lu Tian, Changlin Ran, Ting Chen, Hongming Guddat, Luke W. Liu, Fengjiang Gao, Yan Rao, Zihe Gong, Hongri |
author_facet | Du, Zhanqiang Zhou, Xiaoting Lai, Yuezheng Xu, Jinxu Zhang, Yuying Zhou, Shan Feng, Ziyan Yu, Long Tang, Yanting Wang, Weiwei Yu, Lu Tian, Changlin Ran, Ting Chen, Hongming Guddat, Luke W. Liu, Fengjiang Gao, Yan Rao, Zihe Gong, Hongri |
author_sort | Du, Zhanqiang |
collection | PubMed |
description | Human complex II is a key protein complex that links two essential energy-producing processes: the tricarboxylic acid cycle and oxidative phosphorylation. Deficiencies due to mutagenesis have been shown to cause mitochondrial disease and some types of cancers. However, the structure of this complex is yet to be resolved, hindering a comprehensive understanding of the functional aspects of this molecular machine. Here, we have determined the structure of human complex II in the presence of ubiquinone at 2.86 Å resolution by cryoelectron microscopy, showing it comprises two water-soluble subunits, SDHA and SDHB, and two membrane-spanning subunits, SDHC and SDHD. This structure allows us to propose a route for electron transfer. In addition, clinically relevant mutations are mapped onto the structure. This mapping provides a molecular understanding to explain why these variants have the potential to produce disease. |
format | Online Article Text |
id | pubmed-10161127 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-101611272023-05-06 Structure of the human respiratory complex II Du, Zhanqiang Zhou, Xiaoting Lai, Yuezheng Xu, Jinxu Zhang, Yuying Zhou, Shan Feng, Ziyan Yu, Long Tang, Yanting Wang, Weiwei Yu, Lu Tian, Changlin Ran, Ting Chen, Hongming Guddat, Luke W. Liu, Fengjiang Gao, Yan Rao, Zihe Gong, Hongri Proc Natl Acad Sci U S A Biological Sciences Human complex II is a key protein complex that links two essential energy-producing processes: the tricarboxylic acid cycle and oxidative phosphorylation. Deficiencies due to mutagenesis have been shown to cause mitochondrial disease and some types of cancers. However, the structure of this complex is yet to be resolved, hindering a comprehensive understanding of the functional aspects of this molecular machine. Here, we have determined the structure of human complex II in the presence of ubiquinone at 2.86 Å resolution by cryoelectron microscopy, showing it comprises two water-soluble subunits, SDHA and SDHB, and two membrane-spanning subunits, SDHC and SDHD. This structure allows us to propose a route for electron transfer. In addition, clinically relevant mutations are mapped onto the structure. This mapping provides a molecular understanding to explain why these variants have the potential to produce disease. National Academy of Sciences 2023-04-25 2023-05-02 /pmc/articles/PMC10161127/ /pubmed/37098072 http://dx.doi.org/10.1073/pnas.2216713120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Du, Zhanqiang Zhou, Xiaoting Lai, Yuezheng Xu, Jinxu Zhang, Yuying Zhou, Shan Feng, Ziyan Yu, Long Tang, Yanting Wang, Weiwei Yu, Lu Tian, Changlin Ran, Ting Chen, Hongming Guddat, Luke W. Liu, Fengjiang Gao, Yan Rao, Zihe Gong, Hongri Structure of the human respiratory complex II |
title | Structure of the human respiratory complex II |
title_full | Structure of the human respiratory complex II |
title_fullStr | Structure of the human respiratory complex II |
title_full_unstemmed | Structure of the human respiratory complex II |
title_short | Structure of the human respiratory complex II |
title_sort | structure of the human respiratory complex ii |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10161127/ https://www.ncbi.nlm.nih.gov/pubmed/37098072 http://dx.doi.org/10.1073/pnas.2216713120 |
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