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Schlagwörter:
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Zusammenfassung:
Mitochondrial NADH:ubiquinone oxidoreductase (complex I) is a 1-MDa membrane protein complex with a cen-
tral role in energy metabolism. Redox-driven proton translocation by complex I contributes substantially to the
proton motive force that drives ATP synthase. Several structures of complex I from bacteria and mitochondria
have been determined, but its catalytic mechanism has remained controversial. We here present the cryo-EM
structure of complex I from Yarrowia lipolytica at 2.1-Å resolution, which reveals the positions of more than 1600
protein-bound water molecules, of which ~100 are located in putative proton translocation pathways. Another
structure of the same complex under steady-state activity conditions at 3.4-Å resolution indicates conformational
transitions that we associate with proton injection into the central hydrophilic axis. By combining high-resolution
structural data with site-directed mutagenesis and large-scale molecular dynamic simulations, we define details
of the proton translocation pathways and offer insights into the redox-coupled proton pumping mechanism
of complex I.
