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Title | Cryo-EM structures define ubiquinone-10 binding to mitochondrial complex I and conformational transitions accompanying Q-site occupancy. |
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Journal, issue, pages | Nat Commun, Vol. 13, Issue 1, Page 2758, Year 2022 |
Publish date | May 19, 2022 |
![]() | Injae Chung / John J Wright / Hannah R Bridges / Bozhidar S Ivanov / Olivier Biner / Caroline S Pereira / Guilherme M Arantes / Judy Hirst / ![]() ![]() ![]() |
PubMed Abstract | Mitochondrial complex I is a central metabolic enzyme that uses the reducing potential of NADH to reduce ubiquinone-10 (Q) and drive four protons across the inner mitochondrial membrane, powering ...Mitochondrial complex I is a central metabolic enzyme that uses the reducing potential of NADH to reduce ubiquinone-10 (Q) and drive four protons across the inner mitochondrial membrane, powering oxidative phosphorylation. Although many complex I structures are now available, the mechanisms of Q reduction and energy transduction remain controversial. Here, we reconstitute mammalian complex I into phospholipid nanodiscs with exogenous Q. Using cryo-EM, we reveal a Q molecule occupying the full length of the Q-binding site in the 'active' (ready-to-go) resting state together with a matching substrate-free structure, and apply molecular dynamics simulations to propose how the charge states of key residues influence the Q binding pose. By comparing ligand-bound and ligand-free forms of the 'deactive' resting state (that require reactivating to catalyse), we begin to define how substrate binding restructures the deactive Q-binding site, providing insights into its physiological and mechanistic relevance. |
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Methods | EM (single particle) |
Resolution | 2.3 - 3.02 Å |
Structure data | EMDB-14132, PDB-7qsk: EMDB-14133, PDB-7qsl: EMDB-14134, PDB-7qsm: EMDB-14139, PDB-7qsn: EMDB-14140, PDB-7qso: |
Chemicals | ![]() ChemComp-3PE: ![]() ChemComp-PC1: ![]() ChemComp-SF4: ![]() ChemComp-U10: ![]() ChemComp-FES: ![]() ChemComp-FMN: ![]() ChemComp-K: ![]() ChemComp-CDL: ![]() ChemComp-GTP: ![]() ChemComp-MG: ![]() ChemComp-NDP: ![]() ChemComp-ZN: ![]() ChemComp-EHZ: ![]() ChemComp-CHD: ![]() ChemComp-MYR: ![]() ChemComp-HOH: ![]() ChemComp-GOL: ![]() ChemComp-LMT: |
Source |
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![]() | OXIDOREDUCTASE / Mitochondrial complex I / Respiratory complex I / NADH:ubiquinone oxidoreductase / Ubiquinone / Nanodisc / ELECTRON TRANSPORT |