1. Dissected antiporter modules establish minimal proton-conduction elements of the respiratory complex I.
- Author
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Beghiah A, Saura P, Badolato S, Kim H, Zipf J, Auman D, Gamiz-Hernandez AP, Berg J, Kemp G, and Kaila VRI
- Subjects
- Protein Conformation, Proteolipids metabolism, Proton Pumps metabolism, Oxidative Phosphorylation, Escherichia coli metabolism, Escherichia coli genetics, Bacterial Proteins metabolism, Bacterial Proteins chemistry, Bacterial Proteins genetics, Static Electricity, Models, Molecular, Protons, Electron Transport Complex I metabolism, Electron Transport Complex I chemistry, Electron Transport Complex I genetics, Antiporters metabolism, Antiporters chemistry, Antiporters genetics
- Abstract
The respiratory Complex I is a highly intricate redox-driven proton pump that powers oxidative phosphorylation across all domains of life. Yet, despite major efforts in recent decades, its long-range energy transduction principles remain highly debated. We create here minimal proton-conducting membrane modules by engineering and dissecting the key elements of the bacterial Complex I. By combining biophysical, biochemical, and computational experiments, we show that the isolated antiporter-like modules of Complex I comprise all functional elements required for conducting protons across proteoliposome membranes. We find that the rate of proton conduction is controlled by conformational changes of buried ion-pairs that modulate the reaction barriers by electric field effects. The proton conduction is also modulated by bulky residues along the proton channels that are key for establishing a tightly coupled proton pumping machinery in Complex I. Our findings provide direct experimental evidence that the individual antiporter modules are responsible for the proton transport activity of Complex I. On a general level, our findings highlight electrostatic and conformational coupling mechanisms in the modular energy-transduction machinery of Complex I with distinct similarities to other enzymes., (© 2024. The Author(s).)
- Published
- 2024
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