How inter-subunit contacts in the membrane domain of complex I affect proton transfer energetics

• Published in: Biochimica et biophysica acta. Bioenergetics 2018-09, Vol.1859 (9), p.734-741
• Main Authors: Di Luca, Andrea, Mühlbauer, Max E., Saura, Patricia, Kaila, Ville R.I.
• Format: Article
• Language: English
• Subjects: Bioenergetics; Cell Membrane - metabolism; Electron Transport; Electron Transport Complex I - metabolism; Energy Metabolism; Enzyme dynamics; Models, Molecular; Molecular Dynamics Simulation; NADH:ubiquinone oxidoreductase; Oxidation-Reduction; Protein Conformation; Protein Domains; Protein Subunits; Proton Pumps; Proton transfer; Protons; Thermus thermophilus - metabolism
• ISSN: 0005-2728; 1879-2650
• DOI: 10.1016/j.bbabio.2018.06.001

The respiratory complex I is a redox-driven proton pump that employs the free energy released from quinone reduction to pump protons across its complete ca. 200 Å wide membrane domain. Despite recently resolved structures and molecular simulations, the exact mechanism for the proton transport process remains unclear. Here we combine large-scale molecular simulations with quantum chemical density functional theory (DFT) models to study how contacts between neighboring antiporter-like subunits in the membrane domain of complex I affect the proton transfer energetics. Our combined results suggest that opening of conserved Lys/Glu ion pairs within each antiporter-like subunit modulates the barrier for the lateral proton transfer reactions. Our work provides a mechanistic suggestion for key coupling effects in the long-range force propagation process of complex I. •Residues in antiporter-like subunits alternate between intra- and inter-subunit interactions.•The inter-subunit contacts are stabilized by conserved Lys/Glu ion pairs.•Conformational changes in the ion pairs modulate the proton transfer energetics.•Inter-subunit interactions are key for the long-range force propagation process.