Mammalian Respiratory Complex I Through the Lens of Cryo-EM.

TitleMammalian Respiratory Complex I Through the Lens of Cryo-EM.
Publication TypeJournal Article
Year of Publication2019
AuthorsAgip, A-NA, Blaza, JN, Fedor, JG, Hirst, J
JournalAnnu Rev Biophys
Volume48
Pagination165-184
Date Published2019 May 06
ISSN1936-1238
Abstract

Single-particle electron cryomicroscopy (cryo-EM) has led to a revolution in structural work on mammalian respiratory complex I. Complex I (mitochondrial NADH:ubiquinone oxidoreductase), a membrane-bound redox-driven proton pump, is one of the largest and most complicated enzymes in the mammalian cell. Rapid progress, following the first 5-Å resolution data on bovine complex I in 2014, has led to a model for mouse complex I at 3.3-Å resolution that contains 96% of the 8,518 residues and to the identification of different particle classes, some of which are assigned to biochemically defined states. Factors that helped improve resolution, including improvements to biochemistry, cryo-EM grid preparation, data collection strategy, and image processing, are discussed. Together with recent structural data from an ancient relative, membrane-bound hydrogenase, cryo-EM on mammalian complex I has provided new insights into the proton-pumping machinery and a foundation for understanding the enzyme's catalytic mechanism.

DOI10.1146/annurev-biophys-052118-115704
Alternate JournalAnnu Rev Biophys
Citation Key10.1146/annurev-biophys-052118-115704
PubMed ID30786232
Grant ListMC_U105663141 / / Medical Research Council / United Kingdom