Blaza, James N orcid.org/0000-0001-5420-2116, Vinothkumar, Kutti R and Hirst, Judy (2018) Structure of the Deactive State of Mammalian Respiratory Complex I. Structure. 312-319.e3. ISSN 1878-4186
Abstract
Complex I (NADH:ubiquinone oxidoreductase) is central to energy metabolism in mammalian mitochondria. It couples NADH oxidation by ubiquinone to proton transport across the energy-conserving inner membrane, catalyzing respiration and driving ATP synthesis. In the absence of substrates, active complex I gradually enters a pronounced resting or deactive state. The active-deactive transition occurs during ischemia and is crucial for controlling how respiration recovers upon reperfusion. Here, we set a highly active preparation of Bos taurus complex I into the biochemically defined deactive state, and used single-particle electron cryomicroscopy to determine its structure to 4.1 Å resolution. We show that the deactive state arises when critical structural elements that form the ubiquinone-binding site become disordered, and we propose reactivation is induced when substrate binding to the NADH-reduced enzyme templates their reordering. Our structure both rationalizes biochemical data on the deactive state and offers new insights into its physiological and cellular roles. Blaza et al. used electron cryomicroscopy together with PEGylated gold grids to determine the structure of the deactive state of mammalian complex I, which is formed during ischemia, and showed it is characterized by localized unfolding around the quinone-binding site.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 The Authors |
Keywords: | NADH:ubiquinone oxidoreductase,PEGylated gold grid,cryo-EM,disordered protein structure,electron transport chain,membrane protein,mitochondria |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | Pure (York) |
Date Deposited: | 21 Nov 2018 14:20 |
Last Modified: | 23 Jan 2025 00:16 |
Published Version: | https://doi.org/10.1016/j.str.2017.12.014 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1016/j.str.2017.12.014 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:139001 |
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