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-Structure paper
Title | High-resolution structure and dynamics of mitochondrial complex I-Insights into the proton pumping mechanism. |
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Journal, issue, pages | Sci Adv, Vol. 7, Issue 46, Page eabj3221, Year 2021 |
Publish date | Nov 12, 2021 |
![]() | Kristian Parey / Jonathan Lasham / Deryck J Mills / Amina Djurabekova / Outi Haapanen / Etienne Galemou Yoga / Hao Xie / Werner Kühlbrandt / Vivek Sharma / Janet Vonck / Volker Zickermann / ![]() ![]() |
PubMed Abstract | 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 ...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 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. |
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Methods | EM (single particle) |
Resolution | 2.4 - 3.4 Å |
Structure data | EMDB-12741, PDB-7o6y: EMDB-12742, PDB-7o71: |
Chemicals | ![]() ChemComp-SF4: ![]() ChemComp-FES: ![]() ChemComp-FMN: ![]() ChemComp-NAI: ![]() ChemComp-UQ9: ![]() ChemComp-3PE: ![]() ChemComp-PLC: ![]() ChemComp-CPL: ![]() ChemComp-T7X: ![]() ChemComp-CDL: ![]() ChemComp-NDP: ![]() ChemComp-LMN: ![]() ChemComp-ZN: ![]() ChemComp-ZMP: ![]() ChemComp-HOH: |
Source |
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![]() | OXIDOREDUCTASE / Complex I / NADH dehydrogenase / Mitochondrion proton pumping / Ubiquinone |