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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 |
Authors | 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. |
External links | Sci Adv / PubMed:34767441 / PubMed Central |
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: |
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Keywords | OXIDOREDUCTASE / Complex I / NADH dehydrogenase / Mitochondrion proton pumping / Ubiquinone |