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Structure of the Deactive State of Mammalian Respiratory Complex I

DOI: 10.1016/j.str.2017.12.014 DOI Help

Authors: James N. Blaza (MRC Mitochondrial Biology Unit, University of Cambridge) , Kutti R. Vinothkumar (MRC Laboratory of Molecular Biology) , Judy Hirst (MRC Mitochondrial Biology Unit, University of Cambridge; MRC Laboratory of Molecular Biology)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Structure

State: Published (Approved)
Published: January 2018
Diamond Proposal Number(s): 13581

Open Access Open Access

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.

Journal Keywords: disordered protein structure; electron transport chain; cryo-EM; membrane protein; mitochondria; NADH:ubiquinone oxidoreductase; PEGylated gold grid

Subject Areas: Biology and Bio-materials

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: Krios I-Titan Krios I at Diamond

Added On: 30/01/2018 15:40


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