RT Journal Article
SR Electronic
T1 High-resolution structure and dynamics of mitochondrial complex I – insights into the proton pumping mechanism
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.04.16.440187
DO 10.1101/2021.04.16.440187
A1 Kristian Parey
A1 Jonathan Lasham
A1 Deryck J. Mills
A1 Amina Djurabekova
A1 Outi Haapanen
A1 Etienne Galemou Yoga
A1 Hao Xie
A1 Werner Kühlbrandt
A1 Vivek Sharma
A1 Janet Vonck
A1 Volker Zickermann
YR 2021
UL http://biorxiv.org/content/early/2021/04/16/2021.04.16.440187.abstract
AB Mitochondrial NADH:ubiquinone oxidoreductase (complex I) is a 1 MDa membrane protein complex with a central 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 dynamics simulations, we define details of the proton translocation pathways, and offer new insights into the redox-coupled proton pumping mechanism of complex I.Competing Interest StatementThe authors have declared no competing interest.