We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Long-range charge transfer mechanism of the III<sub>2</sub>IV<sub>2</sub> mycobacterial supercomplex.
- Authors
Riepl, Daniel; Gamiz-Hernandez, Ana P.; Kovalova, Terezia; Król, Sylwia M.; Mader, Sophie L.; Sjöstrand, Dan; Högbom, Martin; Brzezinski, Peter; Kaila, Ville R. I.
- 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 III2IV2 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. The obligate supercomplex from M. Tuberculosis has emerged as a promising drug target. Here the authors employ structural experiments, activity assays, and multiscale molecular simulations, to elucidate the mechanism of charge transfer in this enzyme.
- Subjects
CHARGE transfer; CHARGE exchange; MYCOBACTERIUM smegmatis; PATHOGENIC bacteria; BIOLOGICAL membranes; PROTON transfer reactions
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-49628-9