9QEF

Respiratory supercomplex from Mycobacterium smegmatis with decylubiquinone

Summary for 9QEF

• Entry DOI: 10.2210/pdb9qef/pdb
• EMDB information: 53065
• Descriptor: Cytochrome bc1 complex cytochrome c subunit, Uncharacterized protein MSMEG_4692/MSMEI_4575, LpqE protein, ... (33 entities in total)
• Functional Keywords: respiratory supercomplex, membrane protein, actinobacteria, electron transport
• Biological source: Mycolicibacterium smegmatis; More
• Total number of polymer chains: 28
• Total formula weight: 808260.93

Authors

Kovalova, T.,Krol, S.,Brzezinski, P.,Hogbom, M. (deposition date: 2025-03-09, release date: 2026-01-21)

Primary citation

Krol, S.,Kovalova, T.,Janczak, M.,Kalsum, S.,Akber, M.,Hogbom, M.,Brighenti, S.,Adelroth, P.,Brzezinski, P.
Mycobacterial respiratory chain enzymes and growth are inhibited by decylubiquinone.
Commun Biol, 9:43-43, 2025

PubMed Abstract: Aerobic organisms obtain energy by linking electron transfer from NADH to O, through the respiratory chain, to transmembrane proton translocation. In mycobacteria the respiratory chain is branched; the membrane-bound electron carrier menaquinol (MQH) donates electrons either to the O-reducing cytochrome bd or a supercomplex that is composed of a complex (C) III dimer flanked by two CIVs. Here, we measured the dimethyl-naphthoquinone (DMNQH a menaquinol analogue) oxidation:O reduction activities of the CIIICIV supercomplex and cytochrome bd in the presence of an analogue (decylubiquinone, DCQ) of the mammalian electron carrier, ubiquinol. The data show that DCQH inhibits both the CIIICIV and cytochrome bd activities, suggesting that DCQ/DCQH interferes with both branches of the respiratory chain. Cryo-EM data of the M. smegmatis supercomplex shows that oxidized DCQ binds in the electron donor site (Q) of CIII. Accordingly, growth of M. smegmatis cells was impaired in the presence of DCQ. Remarkably, DCQ also impairs intracellular growth of virulent M. tuberculosis cells in human primary macrophages suggesting that the compound could potentially be used as an adjuvant during tuberculosis disease treatment.

PubMed: 41372535
DOI: 10.1038/s42003-025-09309-9

Experimental method

ELECTRON MICROSCOPY (2.5 Å)