An electron transfer path connects subunits of a mycobacterial respiratory supercomplex

• Published in: Science (American Association for the Advancement of Science) Vol. 362; no. 6418
• Main Authors: Gong, Hongri, Li, Jun, Xu, Ao, Tang, Yanting, Ji, Wenxin, Gao, Ruogu, Wang, Shuhui, Yu, Lu, Tian, Changlin, Li, Jingwen, Yen, Hsin-Yung, Man Lam, Sin, Shui, Guanghou, Yang, Xiuna, Sun, Yuna, Li, Xuemei, Jia, Minze, Yang, Cheng, Jiang, Biao, Lou, Zhiyong, Robinson, Carol V., Wong, Luet-Lok, Guddat, Luke W., Sun, Fei, Wang, Quan, Rao, Zihe
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 30.11.2018
• Subjects: Actinobacteria - enzymology; Bacteria; Bacterial Proteins - chemistry; Binding sites; Cofactors; Corynebacterium glutamicum; Cryoelectron Microscopy; Cytochrome; Cytochrome c; Cytochromes; Detoxification; Dimers; Domains; Drug discovery; Electron microscopy; Electron transfer; Electron Transport; Electron transport chain; Electron Transport Complex III - chemistry; Electron Transport Complex IV - chemistry; Electron tunneling; Gram-negative bacteria; Gram-positive bacteria; Hydroquinone; Immune response; Macromolecules; Macrophages; Membranes; Metabolism; Microscopy; Mitochondria; Molecular structure; Monomers; Mycobacterium smegmatis; Mycobacterium smegmatis - enzymology; Mycobacterium tuberculosis; Oxidation resistance; Oxidation-Reduction; Oxidative Phosphorylation; Oxidative stress; Oxygen; Oxygen - metabolism; Protein Multimerization; Proteins; Protons; Quinones; Reduction; Respiration; Spacecraft components; Superoxide dismutase; Superoxide Dismutase - chemistry; Transmission electron microscopy; Tuberculosis
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.aat8923

Respiratory complexes are massive, membrane-embedded scaffolds that position redox cofactors so as to permit electron transfer coupled to the movement of protons across a membrane. Gong et al. used cryo–electron microscopy to determine a structure of a stable assembly of mycobacterial complex III–IV, in which a complex III dimer is sandwiched between two complex IV monomers. A potential direct electron transfer path stretches from the quinone oxidizing centers in complex III to the oxygen reduction centers in complex IV. A loosely associated superoxide dismutase may play a role in detoxifying superoxide produced from uncoupled oxygen reduction. Science , this issue p. eaat8923 A mycobacterial respiratory supercomplex forgoes soluble electron carriers and associates with superoxide dismutase. 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.