Structure of the human respiratory complex II

被引：25

作者：

Du, Zhanqiang ^{[1
]}

Zhou, Xiaoting ^{[2
]}

Lai, Yuezheng ^{[1
]}

Xu, Jinxu ^{[1
]}

Zhang, Yuying ^{[1
]}

Zhou, Shan ^{[1
]}

Feng, Ziyan ^{[1
]}

Yu, Long ^{[1
,5
]}

Tang, Yanting ^{[1
,5
]}

Wang, Weiwei ^{[3
,4
]}

Yu, Lu

Tian, Changlin

Ran, Ting ^{[6
]}

Chen, Hongming ^{[6
]}

Guddat, Luke W. ^{[7
]}

Liu, Fengjiang ^{[6
]}

Gao, Yan ^{[3
,4
,5
]}

Rao, Zihe ^{[1
,3
,4
,5
,7
,8
,9
]}

Gong, Hongri ^{[1
]}

机构：

[1] Nankai Univ, Coll Life Sci, Frontiers Sci Ctr Cell Responses, State Key Lab Med Chem Biol, Tianjin 300353, Peoples R China

[2] Inner Mongolia Univ, Sch Life Sci, State Key Lab Reprod Regulat & Breeding Grassland, Hohhot 010070, Peoples R China

[3] ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China

[4] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China

[5] Chinese Acad Sci, High Magnet Field Lab, Hefei 230031, Peoples R China

[6] Guangzhou Lab, Innovat Ctr Pathogen Res, Guangzhou 510005, Peoples R China

[7] Univ Queensland, Sch Chem & Mol Biosci, Brisbane, Qld 4072, Australia

[8] Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromolecules, Natl Lab Biomacromolecules, Beijing 100101, Peoples R China

[9] Tsinghua Univ, Lab Struct Biol, Beijing 100084, Peoples R China

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2023年 / 120卷 / 18期

基金：

中国国家自然科学基金;

关键词：

electron transport chain; human complex II; cryoelectron microscopy; SUCCINATE-UBIQUINONE OXIDOREDUCTASE; QUINOL-FUMARATE REDUCTASE; ELECTRON-TRANSFER; CRYSTAL-STRUCTURE; BINDING-SITE; MUTATION; DEHYDROGENASE; HEME; CARDIOMYOPATHY; DEFICIENCY;

D O I：

10.1073/pnas.2216713120

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 & ANGS; 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.

引用

页数：7

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