Journal: Nat Struct Mol Biol / Year: 2020 Title: Mitochondrial complex I structure reveals ordered water molecules for catalysis and proton translocation. Authors: Daniel N Grba / Judy Hirst / Abstract: Mitochondrial complex I powers ATP synthesis by oxidative phosphorylation, exploiting the energy from ubiquinone reduction by NADH to drive protons across the energy-transducing inner membrane. ...Mitochondrial complex I powers ATP synthesis by oxidative phosphorylation, exploiting the energy from ubiquinone reduction by NADH to drive protons across the energy-transducing inner membrane. Recent cryo-EM analyses of mammalian and yeast complex I have revolutionized structural and mechanistic knowledge and defined structures in different functional states. Here, we describe a 2.7-Å-resolution structure of the 42-subunit complex I from the yeast Yarrowia lipolytica containing 275 structured water molecules. We identify a proton-relay pathway for ubiquinone reduction and water molecules that connect mechanistically crucial elements and constitute proton-translocation pathways through the membrane. By comparison with known structures, we deconvolute structural changes governing the mammalian 'deactive transition' (relevant to ischemia-reperfusion injury) and their effects on the ubiquinone-binding site and a connected cavity in ND1. Our structure thus provides important insights into catalysis by this enigmatic respiratory machine.
History
Deposition
Apr 2, 2020
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Header (metadata) release
Aug 12, 2020
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Map release
Aug 12, 2020
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Update
Mar 17, 2021
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Current status
Mar 17, 2021
Processing site: PDBe / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
Model: UltrAuFoil / Material: GOLD / Support film - Material: GOLD / Pretreatment - Type: GLOW DISCHARGE / Details: Gold grids pre-treated with PEG thiol reagent
Vitrification
Cryogen name: ETHANE
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Electron microscopy
Microscope
FEI TITAN KRIOS
Image recording
Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Number grids imaged: 1 / Number real images: 2540 / Average electron dose: 44.0 e/Å2
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
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