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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Published in:Proceedings of the National Academy of Sciences - PNAS 2023-05, Vol.120 (18), p.e2216713120-e2216713120
Main Authors: 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
Format: Article
Language:English
Subjects:
Biological Sciences
Citric Acid Cycle
Cryoelectron Microscopy
Electron transfer
Electron transport
Humans
Mitochondria
Mitochondrial Diseases - genetics
Molecular machines
Molecular structure
Mutagenesis
Mutation
Oxidative phosphorylation
Phosphorylation
Succinate Dehydrogenase - metabolism
Tricarboxylic acid cycle
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2216713120