National Natural Science Foundation of China (NSFC)
31625008, 32030056, 21532004, 31570733, 31800620
China
Citation
Journal: Nat Struct Mol Biol / Year: 2022 Title: The coupling mechanism of mammalian mitochondrial complex I. Authors: Jinke Gu / Tianya Liu / Runyu Guo / Laixing Zhang / Maojun Yang / Abstract: Mammalian respiratory complex I (CI) is a 45-subunit, redox-driven proton pump that generates an electrochemical gradient across the mitochondrial inner membrane to power ATP synthesis in ...Mammalian respiratory complex I (CI) is a 45-subunit, redox-driven proton pump that generates an electrochemical gradient across the mitochondrial inner membrane to power ATP synthesis in mitochondria. In the present study, we report cryo-electron microscopy structures of CI from Sus scrofa in six treatment conditions at a resolution of 2.4-3.5 Å, in which CI structures of each condition can be classified into two biochemical classes (active or deactive), with a notably higher proportion of active CI particles. These structures illuminate how hydrophobic ubiquinone-10 (Q10) with its long isoprenoid tail is bound and reduced in a narrow Q chamber comprising four different Q10-binding sites. Structural comparisons of active CI structures from our decylubiquinone-NADH and rotenone-NADH datasets reveal that Q10 reduction at site 1 is not coupled to proton pumping in the membrane arm, which might instead be coupled to Q10 oxidation at site 2. Our data overturn the widely accepted previous proposal about the coupling mechanism of CI.
History
Deposition
Aug 8, 2021
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Header (metadata) release
Mar 2, 2022
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Map release
Mar 2, 2022
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Update
Mar 2, 2022
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Current status
Mar 2, 2022
Processing site: PDBj / Status: Released
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