TY  - JOUR
A1  - Parey, Kristian Kurt
A1  - Lasham, Jonathan
A1  - Mills, Deryck J.
A1  - Djurabekova, Amina
A1  - Haapanen, Outi
A1  - Galemou Yoga, Etienne
A1  - Xie, Hao
A1  - Kühlbrandt, Werner
A1  - Sharma, Vivek
A1  - Vonck, Janet
A1  - Zickermann, Volker
T1  - High-resolution structure and dynamics of mitochondrial complex I - insights into the proton pumping mechanism
T2  - Science Advances
N2  - 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 dynamic simulations, we define details of the proton translocation pathways and offer insights into the redox-coupled proton pumping mechanism of complex I.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/73415
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-734157
VL  - 7.2021
IS  - 46, eabj3221
SP  - 1
EP  - 12
ER  -