5O31

Mitochondrial complex I in the deactive state

Summary for 5O31

• Entry DOI: 10.2210/pdb5o31/pdb
• EMDB information: 3731
• Descriptor: NADH-ubiquinone oxidoreductase chain 3, NADH-ubiquinone oxidoreductase chain 4L, NADH-ubiquinone oxidoreductase chain 5, ... (49 entities in total)
• Functional Keywords: complex i, redox enzyme, proton pump, membrane protein, oxidoreductase
• Biological source: Bos taurus (Bovine); More
• Total number of polymer chains: 45
• Total formula weight: 932558.78

Authors

Blaza, J.N.,Vinothkumar, K.R.,Hirst, J. (deposition date: 2017-05-23, release date: 2018-01-17, Last modification date: 2019-10-23)

Primary citation

Blaza, J.N.,Vinothkumar, K.R.,Hirst, J.
Structure of the Deactive State of Mammalian Respiratory Complex I.
Structure, 26:312-319.e3, 2018

PubMed 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.

PubMed: 29395787
DOI: 10.1016/j.str.2017.12.014

Experimental method

ELECTRON MICROSCOPY (4.13 Å)