8OVC

Respiratory supercomplex (III2-IV2) from Mycobacterium smegmatis

Summary for 8OVC

• Entry DOI: 10.2210/pdb8ovc/pdb
• EMDB information: 17210
• Descriptor: Cytochrome bc1 complex cytochrome c subunit, Uncharacterized protein MSMEG_4692/MSMEI_4575, LpqE protein, ... (29 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: 766827.18

Authors

Kovalova, T.,Krol, S.,Sjostrand, D.,Riepl, D.,Gamiz-Hernandez, A.,Brzezinski, P.,Kaila, V.,Hogbom, M. (deposition date: 2023-04-25, release date: 2024-07-17)

Primary citation

Riepl, D.,Gamiz-Hernandez, A.P.,Kovalova, T.,Krol, S.M.,Mader, S.L.,Sjostrand, D.,Hogbom, M.,Brzezinski, P.,Kaila, V.R.I.
Long-range charge transfer mechanism of the III 2 IV 2 mycobacterial supercomplex.
Nat Commun, 15:5276-5276, 2024

PubMed Abstract: Aerobic life is powered by membrane-bound redox enzymes that shuttle electrons to oxygen and transfer protons across a biological membrane. Structural studies suggest that these energy-transducing enzymes operate as higher-order supercomplexes, but their functional role remains poorly understood and highly debated. Here we resolve the functional dynamics of the 0.7 MDa IIIIV obligate supercomplex from Mycobacterium smegmatis, a close relative of M. tuberculosis, the causative agent of tuberculosis. By combining computational, biochemical, and high-resolution (2.3 Å) cryo-electron microscopy experiments, we show how the mycobacterial supercomplex catalyses long-range charge transport from its menaquinol oxidation site to the binuclear active site for oxygen reduction. Our data reveal proton and electron pathways responsible for the charge transfer reactions, mechanistic principles of the quinone catalysis, and how unique molecular adaptations, water molecules, and lipid interactions enable the proton-coupled electron transfer (PCET) reactions. Our combined findings provide a mechanistic blueprint of mycobacterial supercomplexes and a basis for developing drugs against pathogenic bacteria.

PubMed: 38902248
DOI: 10.1038/s41467-024-49628-9

Experimental method

ELECTRON MICROSCOPY (2.8 Å)