Electrostatic control of conformational dynamics drives proton translocation in respiratory Complex I
Complex I is a large membrane protein that transduces redox energy into a proton motive force across a biological membrane, powering cellular respiration. Yet, despite significant experimental and computational efforts, its long-range proton translocation mechanism remains poorly understood. Here, we combine nuclear magnetic resonance spectroscopy and site-directed mutagenesis experiments with…
Complex I, a massive membrane protein, converts redox energy into a proton gradient across a cell membrane, fueling cellular respiration. However, the precise mechanism behind its long-range proton transport has remained elusive despite extensive research. To unravel this mystery, scientists combined nuclear magnetic resonance spectroscopy, site-directed mutagenesis, and multiscale simulations to investigate the link between conformational dynamics and proton transfer reactions in the terminal antiporter module of Complex I. Their findings suggest that the protonation of a vital lysine residue (Lys329/His241Nqo12) in this module triggers conformational changes that open the proton pathway.
Additionally, buried ion pairs play a crucial role in controlling the proton translocation process by modulating the barrier through intrinsic electric field effects. The researchers conclude that bioenergetic machines like Complex I utilize a combination of conformational dynamics and hydration transitions to efficiently drive redox-driven proton pumps.
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