Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 114, Issue 31, Pages E6314-E6321Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1706278114
Keywords
NADH:ubiquinone oxidoreductase; proton pumping; Grotthuss mechanism; multiscale simulation; bioenergetics
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Funding
- German Research Foundation
- SuperMuc at the Leibniz Rechenzentrum [pr48de]
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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-angstrom 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.
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