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TitleStructure of the Deactive State of Mammalian Respiratory Complex I.
Journal, issue, pagesStructure, Vol. 26, Issue 2, Page 312-319.e3, Year 2018
Publish dateFeb 6, 2018
AuthorsJames N Blaza / Kutti R Vinothkumar / Judy Hirst /
PubMed AbstractComplex 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 ...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.
External linksStructure / PubMed:29395787 / PubMed Central
MethodsEM (single particle)
Resolution4.13 - 7.5 Å
Structure data

3731

5o31

EMDB-3731, PDB-5o31:
Mitochondrial complex I in the deactive state
Method: EM (single particle) / Resolution: 4.13 Å

EMDB-3733:
Minor class in a preparation of mitochondrial complex I set in the deactive state
Method: EM (single particle) / Resolution: 7.5 Å

Chemicals

ChemComp-SF4:
IRON/SULFUR CLUSTER

ChemComp-FES:
FE2/S2 (INORGANIC) CLUSTER

ChemComp-FMN:
FLAVIN MONONUCLEOTIDE

ChemComp-NAP:
NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE

ChemComp-ZN:
Unknown entry

Source
  • bos taurus (cattle)
  • Bovine (cattle)
KeywordsOXIDOREDUCTASE / Complex I / redox enzyme / proton pump / membrane protein

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