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Open data
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Basic information
Entry | Database: PDB / ID: 6g72 | ||||||||||||
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Title | Mouse mitochondrial complex I in the deactive state | ||||||||||||
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![]() | OXIDOREDUCTASE / Complex I / mitochondria / proton pump / membrane protein | ||||||||||||
Function / homology | ![]() response to injury involved in regulation of muscle adaptation / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / reproductive system development / Mitochondrial protein import / Respiratory electron transport / RHOG GTPase cycle / protein insertion into mitochondrial inner membrane / circulatory system development ...response to injury involved in regulation of muscle adaptation / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / reproductive system development / Mitochondrial protein import / Respiratory electron transport / RHOG GTPase cycle / protein insertion into mitochondrial inner membrane / circulatory system development / blastocyst hatching / respiratory system process / psychomotor behavior / Mitochondrial protein degradation / cellular response to oxygen levels / iron-sulfur cluster assembly complex / response to light intensity / mitochondrial large ribosomal subunit binding / gliogenesis / neural precursor cell proliferation / cardiac muscle tissue development / negative regulation of non-canonical NF-kappaB signal transduction / : / [2Fe-2S] cluster assembly / oxygen sensor activity / adult walking behavior / cellular response to glucocorticoid stimulus / ubiquinone-6 biosynthetic process / positive regulation of mitochondrial membrane potential / respiratory chain complex I / response to hydroperoxide / cellular respiration / iron-sulfur cluster assembly / NADH dehydrogenase activity / mitochondrial ribosome / adult behavior / dopamine metabolic process / positive regulation of ATP biosynthetic process / mitochondrial translation / NADH:ubiquinone reductase (H+-translocating) / positive regulation of execution phase of apoptosis / apoptotic mitochondrial changes / mitochondrial ATP synthesis coupled electron transport / : / mitochondrial electron transport, NADH to ubiquinone / mitochondrial respiratory chain complex I assembly / proton motive force-driven mitochondrial ATP synthesis / acyl binding / ubiquinone binding / NADH dehydrogenase (ubiquinone) activity / acyl carrier activity / cellular response to interferon-beta / neuron development / quinone binding / electron transport coupled proton transport / ATP synthesis coupled electron transport / negative regulation of intrinsic apoptotic signaling pathway / muscle contraction / negative regulation of reactive oxygen species biosynthetic process / ATP metabolic process / cellular response to retinoic acid / extrinsic apoptotic signaling pathway / tricarboxylic acid cycle / : / visual perception / ionotropic glutamate receptor binding / aerobic respiration / Neutrophil degranulation / respiratory electron transport chain / reactive oxygen species metabolic process / neurogenesis / cerebellum development / response to hormone / regulation of mitochondrial membrane potential / mitochondrion organization / fatty acid metabolic process / response to cocaine / kidney development / synaptic membrane / mitochondrial membrane / apoptotic signaling pathway / electron transport chain / sensory perception of sound / regulation of protein phosphorylation / response to nicotine / brain development / response to hydrogen peroxide / multicellular organism growth / response to organic cyclic compound / mitochondrial intermembrane space / negative regulation of cell growth / cognition / 2 iron, 2 sulfur cluster binding / circadian rhythm / positive regulation of protein catabolic process / NAD binding / FMN binding / myelin sheath / nervous system development / 4 iron, 4 sulfur cluster binding Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å | ||||||||||||
![]() | Agip, A.N.A. / Blaza, J.N. / Bridges, H.R. / Viscomi, C. / Rawson, S. / Muench, S.P. / Hirst, J. | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM structures of complex I from mouse heart mitochondria in two biochemically defined states. Authors: Ahmed-Noor A Agip / James N Blaza / Hannah R Bridges / Carlo Viscomi / Shaun Rawson / Stephen P Muench / Judy Hirst / ![]() Abstract: Complex I (NADH:ubiquinone oxidoreductase) uses the reducing potential of NADH to drive protons across the energy-transducing inner membrane and power oxidative phosphorylation in mammalian ...Complex I (NADH:ubiquinone oxidoreductase) uses the reducing potential of NADH to drive protons across the energy-transducing inner membrane and power oxidative phosphorylation in mammalian mitochondria. Recent cryo-EM analyses have produced near-complete models of all 45 subunits in the bovine, ovine and porcine complexes and have identified two states relevant to complex I in ischemia-reperfusion injury. Here, we describe the 3.3-Å structure of complex I from mouse heart mitochondria, a biomedically relevant model system, in the 'active' state. We reveal a nucleotide bound in subunit NDUFA10, a nucleoside kinase homolog, and define mechanistically critical elements in the mammalian enzyme. By comparisons with a 3.9-Å structure of the 'deactive' state and with known bacterial structures, we identify differences in helical geometry in the membrane domain that occur upon activation or that alter the positions of catalytically important charged residues. Our results demonstrate the capability of cryo-EM analyses to challenge and develop mechanistic models for mammalian complex I. | ||||||||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 1.4 MB | Display | ![]() |
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PDB format | ![]() | 1.1 MB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 4356MC ![]() 4345C ![]() 6g2jC C: citing same article ( M: map data used to model this data |
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Similar structure data | |
EM raw data | ![]() Data size: 2.7 TB Data #1: Single particle cryo-EM dataset of Mus musculus mitochondrial complex I in the deactive state [micrographs - multiframe]) |
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Links
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Assembly
Deposited unit | ![]()
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Components
-NADH-ubiquinone oxidoreductase chain ... , 7 types, 7 molecules AHJKLMN
#1: Protein | Mass: 13251.785 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: P03899, NADH:ubiquinone reductase (H+-translocating) |
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#8: Protein | Mass: 36105.027 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: P03888, NADH:ubiquinone reductase (H+-translocating) |
#10: Protein | Mass: 18656.100 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: P03925, NADH:ubiquinone reductase (H+-translocating) |
#11: Protein | Mass: 10637.629 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: P03903, NADH:ubiquinone reductase (H+-translocating) |
#12: Protein | Mass: 68547.297 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: P03921, NADH:ubiquinone reductase (H+-translocating) |
#13: Protein | Mass: 51943.547 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: P03911, NADH:ubiquinone reductase (H+-translocating) |
#14: Protein | Mass: 38800.230 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: P03893, NADH:ubiquinone reductase (H+-translocating) |
-NADH dehydrogenase [ubiquinone] iron-sulfur protein ... , 7 types, 7 molecules BCDIQRe
#2: Protein | Mass: 24715.912 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: Q9DC70, NADH:ubiquinone reductase (H+-translocating), NADH dehydrogenase |
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#3: Protein | Mass: 30191.307 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: Q9DCT2, NADH:ubiquinone reductase (H+-translocating), NADH dehydrogenase |
#4: Protein | Mass: 52720.602 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: Q91WD5, NADH:ubiquinone reductase (H+-translocating), NADH dehydrogenase |
#9: Protein | Mass: 24068.355 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: Q8K3J1, NADH:ubiquinone reductase (H+-translocating), NADH dehydrogenase |
#17: Protein | Mass: 19814.725 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#18: Protein | Mass: 13041.828 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#30: Protein | Mass: 12675.772 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-NADH dehydrogenase [ubiquinone] flavoprotein ... , 3 types, 3 molecules EFs
#5: Protein | Mass: 27318.336 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: Q9D6J6, NADH:ubiquinone reductase (H+-translocating), NADH dehydrogenase |
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#6: Protein | Mass: 50904.152 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: Q91YT0, NADH:ubiquinone reductase (H+-translocating), NADH dehydrogenase |
#44: Protein | Mass: 11833.504 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-Protein , 3 types, 4 molecules GTUY
#7: Protein | Mass: 79866.688 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: Q91VD9, NADH:ubiquinone reductase (H+-translocating), NADH dehydrogenase | ||
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#20: Protein | Mass: 17390.289 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #24: Protein | | Mass: 15130.416 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit ... , 11 types, 11 molecules OPSVWXZabqr
#15: Protein | Mass: 40657.375 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#16: Protein | Mass: 42588.129 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#19: Protein | Mass: 10932.675 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#21: Protein | Mass: 13380.719 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#22: Protein | Mass: 15311.858 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#23: Protein | Mass: 20025.127 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#25: Protein | Mass: 16881.588 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#26: Protein | Mass: 8149.524 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#27: Protein | Mass: 9380.904 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#42: Protein | Mass: 17112.416 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#43: Protein | Mass: 12637.629 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-NADH dehydrogenase [ubiquinone] 1 subunit ... , 2 types, 2 molecules cd
#28: Protein | Mass: 8636.023 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#29: Protein | Mass: 14185.692 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit ... , 11 types, 11 molecules fghijklmnop
#31: Protein | Mass: 6965.109 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#32: Protein | Mass: 17463.727 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#33: Protein | Mass: 21742.197 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#34: Protein | Mass: 15582.122 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#35: Protein | Mass: 11982.437 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#36: Protein | Mass: 11714.240 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#37: Protein | Mass: 21903.828 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#38: Protein | Mass: 15105.287 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#39: Protein | Mass: 22020.123 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#40: Protein | Mass: 16360.804 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#41: Protein | Mass: 21054.832 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-Non-polymers , 8 types, 15 molecules ![](data/chem/img/SF4.gif)
![](data/chem/img/FES.gif)
![](data/chem/img/FMN.gif)
![](data/chem/img/ADP.gif)
![](data/chem/img/NDP.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/EHZ.gif)
![](data/chem/img/ACE.gif)
![](data/chem/img/FES.gif)
![](data/chem/img/FMN.gif)
![](data/chem/img/ADP.gif)
![](data/chem/img/NDP.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/EHZ.gif)
![](data/chem/img/ACE.gif)
#45: Chemical | ChemComp-SF4 / #46: Chemical | #47: Chemical | ChemComp-FMN / | #48: Chemical | ChemComp-ADP / | #49: Chemical | ChemComp-NDP / | #50: Chemical | ChemComp-ZN / | #51: Chemical | #52: Chemical | ChemComp-ACE / | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Mitochondrial complex I from mouse in the deactive state Type: COMPLEX Details: Placed in the deactive state by heating to 37degC for 30 mins before isolation Entity ID: #1-#41, #43-#44 / Source: NATURAL | ||||||||||||||||||||
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Molecular weight | Value: 1.0 MDa / Experimental value: NO | ||||||||||||||||||||
Source (natural) | Organism: ![]() ![]() | ||||||||||||||||||||
Buffer solution | pH: 7.14 | ||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: Peak fraction from a gel filtration column- monodisperse and not concentrated. The complex was put into the deactive state by heating at 37degC for 30 mins before isolation in detergent. | ||||||||||||||||||||
Specimen support | Details: Gold was PEGylated prior to use in anaerobic ethanol in 5mM SPT-11P6 (Sensopath Technologies) for two days 0.6/1 holes Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil UltrAuFoil | ||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K / Details: 8-16s blotting. |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Calibrated magnification: 37600 X / Nominal defocus max: 3400 nm / Nominal defocus min: 2200 nm / Cs: 2.7 mm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 15 sec. / Electron dose: 50 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Num. of grids imaged: 1 |
EM imaging optics | Energyfilter name: GIF Quantum LS / Energyfilter upper: 20 eV / Energyfilter lower: 0 eV |
Image scans | Movie frames/image: 30 / Used frames/image: 1-30 |
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Processing
Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement | |||||||||||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 40131 / Details: Manually picked | |||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 17066 / Algorithm: FOURIER SPACE / Symmetry type: POINT | |||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL Details: Used default paramteres in phenix.real_space_refine |