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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2023
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.
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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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