High-resolution structure and dynamics of mitochondrial complex I—Insights into the proton pumping mechanism
| Autor: | Volker Zickermann, Janet Vonck, Jonathan Lasham, Vivek Sharma, Hao Xie, Deryck J. Mills, Etienne Galemou Yoga, Amina Djurabekova, Kristian Parey, Outi Haapanen, Werner Kühlbrandt |
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| Přispěvatelé: | Doctoral Programme in Materials Research and Nanosciences, Materials Physics, Department of Physics |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Proton
Protein subunit Energy metabolism High resolution CRYO-EM 01 natural sciences STOICHIOMETRY 114 Physical sciences Biochemistry 03 medical and health sciences Molecular dynamics Oxidoreductase Structural Biology 0103 physical sciences CRYSTAL-STRUCTURE 030304 developmental biology chemistry.chemical_classification 0303 health sciences Multidisciplinary 010304 chemical physics Chemistry SciAdv r-articles 3. Good health Membrane protein complex MOLECULAR-DYNAMICS NADH SUBUNIT Biophysics FORCE-FIELD VISUALIZATION Biomedicine and Life Sciences ORIENTATION Mitochondrial Complex I TRANSITION Research Article |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| Popis: | Description High-resolution structure and molecular simulations unravel the inner workings of a redox-driven proton pump. 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. |
| Databáze: | OpenAIRE |
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