1. Symmetry-related proton transfer pathways in respiratory complex I.
- Author
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Di Luca, Andrea, Gamiz-Hernandez, Ana P., and Kaila, Ville R. I.
- Subjects
- *
NAD (Coenzyme) , *PROTON transfer reactions , *UBIQUINONES , *BIOENERGETICS , *SIMULATION methods & models - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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