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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-4040 | |||||||||
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Title | Structure of mammalian respiratory Complex I, class1 | |||||||||
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Function / homology | ![]() Complex I biogenesis / RHOG GTPase cycle / cellular response to oxygen levels / mitochondrial large ribosomal subunit binding / Respiratory electron transport / gliogenesis / neural precursor cell proliferation / : / [2Fe-2S] cluster assembly / oxygen sensor activity ...Complex I biogenesis / RHOG GTPase cycle / cellular response to oxygen levels / mitochondrial large ribosomal subunit binding / Respiratory electron transport / gliogenesis / neural precursor cell proliferation / : / [2Fe-2S] cluster assembly / oxygen sensor activity / cellular respiration / Neutrophil degranulation / NADH dehydrogenase activity / Mitochondrial protein degradation / NADH:ubiquinone reductase (H+-translocating) / apoptotic mitochondrial changes / acyl binding / ubiquinone binding / acyl carrier activity / quinone binding / electron transport coupled proton transport / neurogenesis / ATP synthesis coupled electron transport / negative regulation of intrinsic apoptotic signaling pathway / ATP metabolic process / mitochondrial ATP synthesis coupled electron transport / mitochondrial respiratory chain complex I assembly / respiratory electron transport chain / reactive oxygen species metabolic process / regulation of mitochondrial membrane potential / : / mitochondrial electron transport, NADH to ubiquinone / fatty acid binding / NADH dehydrogenase (ubiquinone) activity / apoptotic signaling pathway / mitochondrial membrane / aerobic respiration / mitochondrial intermembrane space / negative regulation of cell growth / 2 iron, 2 sulfur cluster binding / fatty acid biosynthetic process / NAD binding / FMN binding / 4 iron, 4 sulfur cluster binding / response to oxidative stress / oxidoreductase activity / mitochondrial inner membrane / mitochondrial matrix / negative regulation of DNA-templated transcription / ubiquitin protein ligase binding / mitochondrion / nucleoplasm / metal ion binding / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.27 Å | |||||||||
![]() | Vinothkumar KR / Zhu J / Hirst J | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structure of mammalian respiratory complex I. Authors: Jiapeng Zhu / Kutti R Vinothkumar / Judy Hirst / ![]() Abstract: 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 ...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. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 165.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 74.7 KB 74.7 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 12.6 KB | Display | ![]() |
Images | ![]() | 27.8 KB | ||
Others | ![]() ![]() | 139.8 MB 139.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 5ldwMC ![]() 4032C ![]() 4041C ![]() 5lc5C ![]() 5ldxC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.33 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Half map: #1
File | emd_4040_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_4040_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
+Entire : Bovine respiratory Complex I
+Supramolecule #1: Bovine respiratory Complex I
+Macromolecule #1: NADH-ubiquinone oxidoreductase chain 3
+Macromolecule #2: NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial
+Macromolecule #3: NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial
+Macromolecule #4: NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial
+Macromolecule #5: NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial
+Macromolecule #6: NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial
+Macromolecule #7: NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial,NADH...
+Macromolecule #8: NADH-ubiquinone oxidoreductase chain 1
+Macromolecule #9: NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial
+Macromolecule #10: NADH-ubiquinone oxidoreductase chain 6
+Macromolecule #11: NADH-ubiquinone oxidoreductase chain 4L
+Macromolecule #12: NADH-ubiquinone oxidoreductase chain 5
+Macromolecule #13: NADH-ubiquinone oxidoreductase chain 4
+Macromolecule #14: NADH-ubiquinone oxidoreductase chain 2
+Macromolecule #15: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, ND...
+Macromolecule #16: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, NDUFA9
+Macromolecule #17: NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, NDUFS4
+Macromolecule #18: NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, NDUFS6,NAD...
+Macromolecule #19: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2
+Macromolecule #20: Acyl carrier protein, mitochondrial
+Macromolecule #21: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5
+Macromolecule #22: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6
+Macromolecule #23: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8,NADH...
+Macromolecule #24: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11
+Macromolecule #25: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13, ND...
+Macromolecule #26: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1
+Macromolecule #27: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3,NADH...
+Macromolecule #28: NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial
+Macromolecule #29: NADH dehydrogenase [ubiquinone] 1 subunit C2, NDUFC2,NADH dehydro...
+Macromolecule #30: NADH dehydrogenase [ubiquinone] iron-sulfur protein 5
+Macromolecule #31: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1
+Macromolecule #32: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mit...
+Macromolecule #33: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 5, mito...
+Macromolecule #34: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6,NADH ...
+Macromolecule #35: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, NDUFB2
+Macromolecule #36: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3, NDUFB3
+Macromolecule #37: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, NDUFB8
+Macromolecule #38: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4, NDUF...
+Macromolecule #39: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9,NADH ...
+Macromolecule #40: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7
+Macromolecule #41: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10, NDU...
+Macromolecule #42: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12
+Macromolecule #43: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7, NDUFA7
+Macromolecule #44: NADH dehydrogenase [ubiquinone] flavoprotein 3, NDUFV3
+Macromolecule #45: IRON/SULFUR CLUSTER
+Macromolecule #46: FE2/S2 (INORGANIC) CLUSTER
+Macromolecule #47: FLAVIN MONONUCLEOTIDE
+Macromolecule #48: NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
+Macromolecule #49: ZINC ION
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 3.5 mg/mL |
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Buffer | pH: 8 / Component - Concentration: 150.0 mM / Component - Formula: NaCl / Component - Name: sodium chloride / Details: 20 mM TRIS-HCL, 150 mM NaCl, 0.03% CYMAL-7 |
Grid | Model: Quantifoil / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR Details: Holey carbon grids were placed on a filter paper in a glass petridish and pumped for around 5 minutes to remove any residual moisture. The glow of the plasma was observed and glow discharge when it was purple. |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: HOMEMADE PLUNGER Details: The specimen was vitrified in an environmental plunge-freeze apparatus present in a cold room, blot for 12-15 seconds after the diameter of the blotted meniscus ceases to spread and plunged.. |
Details | Enzyme was purified from bovine heart mitochondria. The detergent used for the final step is cymal-7. |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Temperature | Min: 87.5 K / Max: 87.5 K |
Image recording | Film or detector model: FEI FALCON II (4k x 4k) / Detector mode: INTEGRATING / Digitization - Dimensions - Width: 4096 pixel / Digitization - Dimensions - Height: 4096 pixel / Digitization - Sampling interval: 14.0 µm / Digitization - Frames/image: 1-34 / Average exposure time: 2.0 sec. / Average electron dose: 35.0 e/Å2 Details: Images were collected in movie mode at 17 frames per second. Thus each frame has ~1.0 e/A2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 70.0 µm / Calibrated defocus max: 5.5 µm / Calibrated defocus min: 1.8 µm / Calibrated magnification: 105263 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal magnification: 59000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Space: RECIPROCAL / Protocol: OTHER / Overall B value: 83.049 / Target criteria: Maximum likelihood |
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Output model | ![]() PDB-5ldw: |