Symmetry-related proton transfer pathways in respiratory complex I

• Published in: Proceedings of the National Academy of Sciences - PNAS 2017-08, Vol.114 (31), p.E6314-E6321
• Main Authors: Di Luca, Andrea, Gamiz-Hernandez, Ana P., Kaila, Ville R. I.
• Format: Article
• Language: English
• Subjects: Biological Sciences; Channels; Chemical synthesis; Coupling (molecular); Electron transfer; Electron transport chain; Energy; Gram-negative bacteria; Molecules; PNAS Plus; Protonation; Protons; Quinones; Simulation; Site-directed mutagenesis; Symmetry
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1706278114

Complex I functions as the initial electron acceptor in aerobic respiratory chains of most organisms. This gigantic redox-driven enzyme employs the energy from quinone reduction to pump protons across its complete approximately 200-Å membrane domain, thermodynamically driving synthesis of ATP. Despite recently resolved structures from several species, the molecular mechanism by which complex I catalyzes this long-range proton-coupled electron transfer process, however, still remains unclear. We perform here large-scale classical and quantum molecular simulations to study the function of the proton pump in complex I from Thermus thermophilus. The simulations suggest that proton channels are established at symmetry-related locations in four subunits of the membrane domain. The channels open up by formation of quasi one-dimensional water chains that are sensitive to the protonation states of buried residues at structurally conserved broken helix elements. Our combined data provide mechanistic insight into long-range coupling effects and predictions for site-directed mutagenesis experiments.