Structure of mammalian respiratory complex I.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE

Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.

Cryoelectron Microscopy*; Electron Transport Complex I/*chemistry ; Electron Transport Complex I/*ultrastructure ; Protein Subunits/*chemistry; Animals ; Binding Sites ; Biocatalysis ; Cattle ; Cell Hypoxia ; Electron Transport Complex I/metabolism ; Mitochondria, Heart/enzymology ; Models, Molecular ; Movement ; Oxidation-Reduction ; Protein Structure, Tertiary ; Protein Subunits/metabolism ; Protons ; Ubiquinone/metabolism

Complex I (NADH:ubiquinone oxidoreductase), one of the largest membrane-bound enzymes in the cell, powers ATP synthesis in mammalian mitochondria by using the reducing potential of NADH to drive protons across the inner mitochondrial membrane. Mammalian complex I (ref. 1) contains 45 subunits, comprising 14 core subunits that house the catalytic machinery (and are conserved from bacteria to humans) and a mammalian-specific cohort of 31 supernumerary subunits. Knowledge of the structures and functions of the supernumerary subunits is fragmentary. Here we describe a 4.2-Å resolution single-particle electron cryomicroscopy structure of complex I from Bos taurus. We have located and modelled all 45 subunits, including the 31 supernumerary subunits, to provide the entire structure of the mammalian complex. Computational sorting of the particles identified different structural classes, related by subtle domain movements, which reveal conformationally dynamic regions and match biochemical descriptions of the 'active-to-de-active' enzyme transition that occurs during hypoxia. Our structures therefore provide a foundation for understanding complex I assembly and the effects of mutations that cause clinically relevant complex I dysfunctions, give insights into the structural and functional roles of the supernumerary subunits and reveal new information on the mechanism and regulation of catalysis.
Competing Interests: The authors declare no competing financial interests.

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MC_U105663141 United Kingdom MRC_ Medical Research Council; U105184322 United Kingdom Medical Research Council; U105663141 United Kingdom Medical Research Council

0 (Protein Subunits)
0 (Protons)
1339-63-5 (Ubiquinone)
EC 7.1.1.2 (Electron Transport Complex I)

Date Created: 20160812 Date Completed: 20160913 Latest Revision: 20220129

20231215

PMC5027920

10.1038/nature19095

27509854