Structure of the Deactive State of Mammalian Respiratory Complex I

• DOI: 10.1016/j.str.2017.12.014
• Publication Date: 2018-01-26T10:44:51Z
• Authors: James N. Blaza; Kutti R. Vinothkumar; Judy Hirst
• Keywords: Models, Molecular; 0301 basic medicine; 0303 health sciences; Electron Transport Complex I; PEGylated gold grid; Ubiquinone; 1312; 1315; Cryoelectron Microscopy; electron transport chain; Article; Mitochondria; 3. Good health; mitochondria; NADH:ubiquinone oxidoreductase; 03 medical and health sciences; Animals; cryo-EM; Cattle; membrane protein; Oxidation-Reduction; disordered protein structure

Highlights•Preparation of mammalian complex I in the deactive state that forms during ischemia•The structure determined using electron cryomicroscopy•Improved particle densities and orientations obtained PEGylated gold grids•Localized unfolding around quinone-binding site stateSummaryComplex (NADH:ubiquinone oxidoreductase) is central to energy metabolism mitochondria. It couples NADH oxidation by ubiquinone proton transport across energy-conserving inner membrane, catalyzing respiration driving ATP synthesis. In absence substrates, active gradually enters a pronounced resting or state. The active-deactive transition occurs ischemia crucial for controlling how recovers upon reperfusion. Here, we set highly preparation Bos taurus into biochemically defined state, used single-particle cryomicroscopy determine its 4.1 Å resolution. We show arises when critical structural elements form ubiquinone-binding become disordered, propose reactivation induced substrate binding NADH-reduced enzyme templates their reordering. Our both rationalizes biochemical data on offers new insights physiological cellular roles.Graphical abstract