An electron transfer path connects subunits of a mycobacterial respiratory supercomplex

Hongri Gong; Jun Li; Ao Xu; Yanting Tang; Wenxin Ji; Ruogu Gao; Shuhui Wang; Lu Yu; Changlin Tian; Jingwen Li; Hsin-Yung Yen; Sin Man Lam; Guanghou Shui; Xiuna Yang; Yuna Sun; Xuemei Li; Minze Jia; Cheng Yang; Biao Jiang; Zhiyong Lou; Carol V Robinson; Luet-Lok Wong; Luke W Guddat; Fei Sun; Quan Wang; Zihe Rao

doi:10.1126/science.aat8923

An electron transfer path connects subunits of a mycobacterial respiratory supercomplex

Science. 2018 Nov 30;362(6418):eaat8923. doi: 10.1126/science.aat8923. Epub 2018 Oct 25.

Authors

Hongri Gong¹, Jun Li^{2

3}, Ao Xu^{1

4}, Yanting Tang¹, Wenxin Ji^{4

5}, Ruogu Gao^{4

5}, Shuhui Wang^{2

3}, Lu Yu⁶, Changlin Tian^{6

7}, Jingwen Li⁸, Hsin-Yung Yen^{8

9}, Sin Man Lam¹⁰, Guanghou Shui¹⁰, Xiuna Yang^{2

3}, Yuna Sun⁴, Xuemei Li⁴, Minze Jia⁴, Cheng Yang¹, Biao Jiang², Zhiyong Lou¹¹, Carol V Robinson⁸, Luet-Lok Wong¹², Luke W Guddat¹³, Fei Sun^{14

5}, Quan Wang¹⁴, Zihe Rao^{15

2

3

4

11}

Affiliations

¹ State Key Laboratory of Medicinal Chemical Biology and College of Life Science, Nankai University, Tianjin 300353, China.
² Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, 201210, China.
³ CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences (CAS), 320 Yueyang Road, Shanghai 200031, China.
⁴ National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, CAS, Beijing 100101, China.
⁵ University of Chinese Academy of Sciences, Beijing, China.
⁶ High Magnetic Field Laboratory, CAS, Hefei 230031, China.
⁷ Hefei National Laboratory of Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
⁸ Department of Chemistry, University of Oxford, Physical and Theoretical Chemistry Laboratory, South Parks Rd, Oxford, OX1 3QZ, UK.
⁹ OMass Technologies, Begbroke Science Park, Woodstock Rd, Yarnton, Kidlington OX5 1PF, UK.
¹⁰ State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, CAS, Beijing 100101, China.
¹¹ Laboratory of Structural Biology, Tsinghua University, Beijing 100084, China.
¹² Department of Chemistry, University of Oxford, Inorganic Chemistry Laboratory, South Parks Road, Oxford OX1 3QR, UK.
¹³ School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, 4072 Queensland, Australia.
¹⁴ National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, CAS, Beijing 100101, China. raozh@tsinghua.edu.cn wangq@ibp.ac.cn feisun@ibp.ac.cn.
¹⁵ State Key Laboratory of Medicinal Chemical Biology and College of Life Science, Nankai University, Tianjin 300353, China. raozh@tsinghua.edu.cn wangq@ibp.ac.cn feisun@ibp.ac.cn.

PMID: 30361386
DOI: 10.1126/science.aat8923

Abstract

We report a 3.5-angstrom-resolution cryo-electron microscopy structure of a respiratory supercomplex isolated from Mycobacterium smegmatis. It comprises a complex III dimer flanked on either side by individual complex IV subunits. Complex III and IV associate so that electrons can be transferred from quinol in complex III to the oxygen reduction center in complex IV by way of a bridging cytochrome subunit. We observed a superoxide dismutase-like subunit at the periplasmic face, which may be responsible for detoxification of superoxide formed by complex III. The structure reveals features of an established drug target and provides a foundation for the development of treatments for human tuberculosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actinobacteria / enzymology
Bacterial Proteins / chemistry*
Cryoelectron Microscopy
Electron Transport Complex III / chemistry*
Electron Transport Complex IV / chemistry*
Electron Transport*
Mycobacterium smegmatis / enzymology*
Oxidation-Reduction
Oxidative Phosphorylation
Oxygen / metabolism
Protein Multimerization
Superoxide Dismutase / chemistry*

Substances

Bacterial Proteins
Superoxide Dismutase
superoxide dismutase 2
Electron Transport Complex IV
Electron Transport Complex III
Oxygen