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Open data
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Basic information
Entry | Database: PDB / ID: 5lnk | ||||||
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Title | Entire ovine respiratory complex I | ||||||
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![]() | OXIDOREDUCTASE / NADH:ubiquinone / complex I / mammalian / mitochondrial | ||||||
Function / homology | ![]() Complex I biogenesis / Respiratory electron transport / : / oxidoreductase activity, acting on NAD(P)H / NADH dehydrogenase activity / Mitochondrial protein degradation / NADH:ubiquinone reductase (H+-translocating) / apoptotic mitochondrial changes / acyl binding / ubiquinone binding ...Complex I biogenesis / Respiratory electron transport / : / oxidoreductase activity, acting on NAD(P)H / 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 / : / ATP synthesis coupled electron transport / 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 / NADH dehydrogenase (ubiquinone) activity / apoptotic signaling pathway / electron transport chain / circadian rhythm / aerobic respiration / mitochondrial intermembrane space / negative regulation of cell growth / 2 iron, 2 sulfur cluster binding / NAD binding / FMN binding / 4 iron, 4 sulfur cluster binding / response to oxidative stress / membrane => GO:0016020 / mitochondrial inner membrane / mitochondrial matrix / negative regulation of DNA-templated transcription / protein-containing complex binding / mitochondrion / nucleoplasm / metal ion binding / cytoplasm Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å | ||||||
![]() | Fiedorczuk, K. / Letts, J.A. / Kaszuba, K. / Sazanov, L.A. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Atomic structure of the entire mammalian mitochondrial complex I. Authors: Karol Fiedorczuk / James A Letts / Gianluca Degliesposti / Karol Kaszuba / Mark Skehel / Leonid A Sazanov / ![]() ![]() Abstract: Mitochondrial complex I (also known as NADH:ubiquinone oxidoreductase) contributes to cellular energy production by transferring electrons from NADH to ubiquinone coupled to proton translocation ...Mitochondrial complex I (also known as NADH:ubiquinone oxidoreductase) contributes to cellular energy production by transferring electrons from NADH to ubiquinone coupled to proton translocation across the membrane. It is the largest protein assembly of the respiratory chain with a total mass of 970 kilodaltons. Here we present a nearly complete atomic structure of ovine (Ovis aries) mitochondrial complex I at 3.9 Å resolution, solved by cryo-electron microscopy with cross-linking and mass-spectrometry mapping experiments. All 14 conserved core subunits and 31 mitochondria-specific supernumerary subunits are resolved within the L-shaped molecule. The hydrophilic matrix arm comprises flavin mononucleotide and 8 iron-sulfur clusters involved in electron transfer, and the membrane arm contains 78 transmembrane helices, mostly contributed by antiporter-like subunits involved in proton translocation. Supernumerary subunits form an interlinked, stabilizing shell around the conserved core. Tightly bound lipids (including cardiolipins) further stabilize interactions between the hydrophobic subunits. Subunits with possible regulatory roles contain additional cofactors, NADPH and two phosphopantetheine molecules, which are shown to be involved in inter-subunit interactions. We observe two different conformations of the complex, which may be related to the conformationally driven coupling mechanism and to the active-deactive transition of the enzyme. Our structure provides insight into the mechanism, assembly, maturation and dysfunction of mitochondrial complex I, and allows detailed molecular analysis of disease-causing mutations. | ||||||
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 | ![]() | 1.2 MB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 4093MC ![]() 4084C ![]() 4090C ![]() 4091C M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
+Mitochondrial complex I, ... , 42 types, 42 molecules 1234569HNAMKLJabcdefghiklmnopq...
-Protein , 2 types, 3 molecules jXv
#24: Protein | Mass: 10119.541 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #36: Protein | | Mass: 18818.070 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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-Non-polymers , 10 types, 25 molecules ![](data/chem/img/SF4.gif)
![](data/chem/img/FMN.gif)
![](data/chem/img/FES.gif)
![](data/chem/img/3PE.gif)
![](data/chem/img/PC1.gif)
![](data/chem/img/CDL.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/NDP.gif)
![](data/chem/img/ZMP.gif)
![](data/chem/img/PNS.gif)
![](data/chem/img/FMN.gif)
![](data/chem/img/FES.gif)
![](data/chem/img/3PE.gif)
![](data/chem/img/PC1.gif)
![](data/chem/img/CDL.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/NDP.gif)
![](data/chem/img/ZMP.gif)
![](data/chem/img/PNS.gif)
#45: Chemical | ChemComp-SF4 / #46: Chemical | ChemComp-FMN / | #47: Chemical | #48: Chemical | ChemComp-3PE / #49: Chemical | ChemComp-PC1 / #50: Chemical | ChemComp-CDL / #51: Chemical | ChemComp-ZN / | #52: Chemical | ChemComp-NDP / | #53: Chemical | ChemComp-ZMP / | #54: Chemical | ChemComp-PNS / | |
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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 / Type: COMPLEX / Entity ID: #1-#44 / Source: NATURAL | ||||||||||||||||||||||||||||||
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Molecular weight | Value: 0.97 MDa / Experimental value: YES | ||||||||||||||||||||||||||||||
Source (natural) | Organism: ![]() ![]() | ||||||||||||||||||||||||||||||
Buffer solution | pH: 7.4 | ||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R0.6/1 | ||||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 90 % / Chamber temperature: 277 K / Details: 34s 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 / Nominal magnification: 59000 X / Calibrated magnification: 100720 X / Nominal defocus max: 3500 nm / Nominal defocus min: 500 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: 1 sec. / Electron dose: 26 e/Å2 / Detector mode: INTEGRATING / Film or detector model: FEI FALCON II (4k x 4k) / Num. of grids imaged: 2 / Num. of real images: 2600 |
Image scans | Sampling size: 14 µm / Width: 4096 / Height: 4096 / Movie frames/image: 7 / Used frames/image: 1-7 |
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Processing
Software | Name: PHENIX / Version: 1.10_2148: / 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: 241000 | ||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 82000 / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL | ||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 4HEA Details: For the fourteen core subunits we used as a starting point our previous structure from T. thermophilus (PDB 4HEA) with sequence adjusted to ovine and side-chains rebuilt in SQWRL4. These are ...Details: For the fourteen core subunits we used as a starting point our previous structure from T. thermophilus (PDB 4HEA) with sequence adjusted to ovine and side-chains rebuilt in SQWRL4. These are chains 1, 2, 3, 4, 5, 6, 9, H, A, J, K, N, M and L (with the same chain IDs as in 4HEA). For the remaining supernumerary subunits it was mostly de novo building with some help from homology modeling, which in most cases was not very useful due to low sequence homology. In few cases models produced by Phyre2 server were useful and were used as a starting point, due to the presence of templates with high coverage and confidence: 42kDa (chain k) - PDB ID 1P6X (xray) 39kDa (chain d) - PDB ID 3WJ7 (xray) SDAPs (chains j and X) - PDB ID 2DNW (NMR) B8 (chain e) - PDB ID 1S3A (NMR) | ||||||||||||||||||||||||||||||||
Refinement | Highest resolution: 3.9 Å | ||||||||||||||||||||||||||||||||
Refine LS restraints |
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