High-resolution structure and dynamics of mitochondrial complex I-Insights into the proton pumping mechanism
Autor(en): | Parey, Kristian Lasham, Jonathan Mills, Deryck J. Djurabekova, Amina Haapanen, Outi Yoga, Etienne Galemou Xie, Hao Kuhlbrandt, Werner Sharma, Vivek Vonck, Janet Zickermann, Volker |
Stichwörter: | CRYO-EM; CRYSTAL-STRUCTURE; FORCE-FIELD; MOLECULAR-DYNAMICS; Multidisciplinary Sciences; NADH; ORIENTATION; Science & Technology - Other Topics; STOICHIOMETRY; SUBUNIT; TRANSITION; VISUALIZATION | Erscheinungsdatum: | 2021 | Herausgeber: | AMER ASSOC ADVANCEMENT SCIENCE | Journal: | SCIENCE ADVANCES | Volumen: | 7 | Ausgabe: | 46 | Zusammenfassung: | 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-angstrom resolution, which reveals the positions of more than 1600 protein-bound water molecules, of which similar to 100 are located in putative proton translocation pathways. Another structure of the same complex under steady-state activity conditions at 3.4-angstrom 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. |
ISSN: | 23752548 | DOI: | 10.1126/sciadv.abj3221 |
Show full item record