Mammalian Respiratory Complex I Through the Lens of Cryo-EM

Ahmed-Noor A Agip; James N Blaza; Justin G Fedor; Judy Hirst

doi:10.1146/annurev-biophys-052118-115704

Mammalian Respiratory Complex I Through the Lens of Cryo-EM

Ahmed-Noor A Agip, James N Blaza, Justin G Fedor, Judy Hirst

Chemistry

Research output: Contribution to journal › Review article › peer-review

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.

Original language	English
Pages (from-to)	165-184
Number of pages	20
Journal	Annual review of biophysics
Volume	48
Early online date	20 Feb 2019
DOIs	https://doi.org/10.1146/annurev-biophys-052118-115704
Publication status	Published - 6 May 2019

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10.1146/annurev-biophys-052118-115704

Cite this

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title = "Mammalian Respiratory Complex I Through the Lens of Cryo-EM",

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-{\AA} resolution data on bovine complex I in 2014, has led to a model for mouse complex I at 3.3-{\AA} 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.",

author = "Agip, {Ahmed-Noor A} and Blaza, {James N} and Fedor, {Justin G} and Judy Hirst",

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doi = "10.1146/annurev-biophys-052118-115704",

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T1 - Mammalian Respiratory Complex I Through the Lens of Cryo-EM

AU - Agip, Ahmed-Noor A

AU - Blaza, James N

AU - Fedor, Justin G

AU - Hirst, Judy

PY - 2019/5/6

Y1 - 2019/5/6

N2 - 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.

AB - 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.

U2 - 10.1146/annurev-biophys-052118-115704

DO - 10.1146/annurev-biophys-052118-115704

M3 - Review article

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SN - 1936-122X

VL - 48

SP - 165

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JO - Annual review of biophysics

JF - Annual review of biophysics

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