|Title||Structure of the Deactive State of Mammalian Respiratory Complex I.|
|Publication Type||Journal Article|
|Year of Publication||2018|
|Authors||Blaza, JN, Vinothkumar, KR, Hirst, J|
|Date Published||2018 Feb 06|
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.
|PubMed Central ID||PMC5807054|
|Grant List||/ / Wellcome Trust / United Kingdom|