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- PDB-8c2s: Cryo-EM structure NDUFS4 knockout complex I from Mus musculus hea... -
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Basic information
Entry | Database: PDB / ID: 8c2s | ||||||||||||
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Title | Cryo-EM structure NDUFS4 knockout complex I from Mus musculus heart (Class 1). | ||||||||||||
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![]() | OXIDOREDUCTASE / NADH ubiquinone oxidoreductase / Complex I | ||||||||||||
Function / homology | ![]() Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / reproductive system development / Mitochondrial protein import / Respiratory electron transport / Glyoxylate metabolism and glycine degradation / RHOG GTPase cycle / blastocyst hatching / circulatory system development / response to light intensity ...Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / reproductive system development / Mitochondrial protein import / Respiratory electron transport / Glyoxylate metabolism and glycine degradation / RHOG GTPase cycle / blastocyst hatching / circulatory system development / response to light intensity / protein insertion into mitochondrial inner membrane / Mitochondrial protein degradation / cellular response to oxygen levels / iron-sulfur cluster assembly complex / mitochondrial large ribosomal subunit binding / gliogenesis / neural precursor cell proliferation / cardiac muscle tissue development / : / [2Fe-2S] cluster assembly / oxygen sensor activity / respiratory chain complex I / cellular response to glucocorticoid stimulus / deoxynucleoside kinase activity / negative regulation of non-canonical NF-kappaB signal transduction / positive regulation of mitochondrial membrane potential / response to hydroperoxide / cellular respiration / ubiquinone-6 biosynthetic process / iron-sulfur cluster assembly / mitochondrial ribosome / positive regulation of ATP biosynthetic process / mitochondrial translation / NADH:ubiquinone reductase (H+-translocating) / positive regulation of execution phase of apoptosis / apoptotic mitochondrial changes / NADH dehydrogenase activity / mitochondrial ATP synthesis coupled electron transport / : / mitochondrial electron transport, NADH to ubiquinone / proton motive force-driven mitochondrial ATP synthesis / ubiquinone binding / mitochondrial respiratory chain complex I assembly / acyl binding / NADH dehydrogenase (ubiquinone) activity / cellular response to interferon-beta / acyl carrier activity / quinone binding / electron transport coupled proton transport / ATP synthesis coupled electron transport / negative regulation of reactive oxygen species biosynthetic process / cellular response to retinoic acid / extrinsic apoptotic signaling pathway / negative regulation of intrinsic apoptotic signaling pathway / ATP metabolic process / : / aerobic respiration / Neutrophil degranulation / respiratory electron transport chain / reactive oxygen species metabolic process / mitochondrion organization / cerebellum development / neurogenesis / regulation of mitochondrial membrane potential / response to hormone / response to cocaine / fatty acid metabolic process / synaptic membrane / kidney development / muscle contraction / mitochondrial membrane / apoptotic signaling pathway / electron transport chain / ionotropic glutamate receptor binding / response to nicotine / response to hydrogen peroxide / multicellular organism growth / response to organic cyclic compound / mitochondrial intermembrane space / negative regulation of cell growth / 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 / response to ethanol / protease binding / in utero embryonic development / response to oxidative stress / mitochondrial inner membrane / electron transfer activity / nuclear body / response to hypoxia / nuclear speck / structural constituent of ribosome / mitochondrial matrix / response to xenobiotic stimulus Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å | ||||||||||||
![]() | Yin, Z. / Bridges, H.R. / Agip, A.N.A. / Hirst, J. | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural insights into respiratory complex I deficiency and assembly from the mitochondrial disease-related ndufs4 mouse. Authors: Zhan Yin / Ahmed-Noor A Agip / Hannah R Bridges / Judy Hirst / ![]() ![]() ![]() Abstract: Respiratory complex I (NADH:ubiquinone oxidoreductase) is essential for cellular energy production and NAD homeostasis. Complex I mutations cause neuromuscular, mitochondrial diseases, such as Leigh ...Respiratory complex I (NADH:ubiquinone oxidoreductase) is essential for cellular energy production and NAD homeostasis. Complex I mutations cause neuromuscular, mitochondrial diseases, such as Leigh Syndrome, but their molecular-level consequences remain poorly understood. Here, we use a popular complex I-linked mitochondrial disease model, the ndufs4 mouse, to define the structural, biochemical, and functional consequences of the absence of subunit NDUFS4. Cryo-EM analyses of the complex I from ndufs4 mouse hearts revealed a loose association of the NADH-dehydrogenase module, and discrete classes containing either assembly factor NDUFAF2 or subunit NDUFS6. Subunit NDUFA12, which replaces its paralogue NDUFAF2 in mature complex I, is absent from all classes, compounding the deletion of NDUFS4 and preventing maturation of an NDUFS4-free enzyme. We propose that NDUFAF2 recruits the NADH-dehydrogenase module during assembly of the complex. Taken together, the findings provide new molecular-level understanding of the ndufs4 mouse model and complex I-linked mitochondrial disease. | ||||||||||||
History |
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Structure visualization
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
Summary document | ![]() | 3 MB | Display | ![]() |
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Full document | ![]() | 3 MB | Display | |
Data in XML | ![]() | 210.9 KB | Display | |
Data in CIF | ![]() | 313.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 16398MC ![]() 8ca1C ![]() 8ca3C ![]() 8ca4C ![]() 8ca5C M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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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: 18541.012 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: 68418.180 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 ... , 6 types, 6 molecules BCDIRe
#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) |
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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) |
#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) |
#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) |
#17: Protein | Mass: 13041.828 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#29: 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: 27077.047 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: Q9D6J6, NADH:ubiquinone reductase (H+-translocating) |
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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) |
#42: 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) | ||
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#19: Protein | Mass: 17390.289 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #23: 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 ... , 10 types, 10 molecules OPSVWXZabr
#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) ![]() ![]() |
#18: Protein | Mass: 10932.675 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#20: Protein | Mass: 13380.719 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#21: Protein | Mass: 15311.858 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#22: Protein | Mass: 20025.127 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#24: Protein | Mass: 16881.588 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#25: Protein | Mass: 8149.524 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#26: Protein | Mass: 9338.867 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#41: Protein | Mass: 12595.592 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-NADH dehydrogenase [ubiquinone] 1 subunit ... , 2 types, 2 molecules cd
#27: Protein | Mass: 8636.023 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#28: 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
#30: Protein | Mass: 6965.109 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#31: Protein | Mass: 17463.727 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#32: Protein | Mass: 21742.197 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#33: Protein | Mass: 15450.925 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#34: Protein | Mass: 11982.437 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#35: Protein | Mass: 11714.240 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#36: Protein | Mass: 21903.828 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#37: Protein | Mass: 15105.287 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#38: Protein | Mass: 22020.123 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#39: Protein | Mass: 16360.804 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#40: Protein | Mass: 21054.832 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-Sugars , 1 types, 2 molecules ![](data/chem/img/LMT.gif)
#49: Sugar |
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-Non-polymers , 10 types, 29 molecules ![](data/chem/img/SF4.gif)
![](data/chem/img/PC1.gif)
![](data/chem/img/FES.gif)
![](data/chem/img/FMN.gif)
![](data/chem/img/3PE.gif)
![](data/chem/img/CDL.gif)
![](data/chem/img/GTP.gif)
![](data/chem/img/NAP.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/EHZ.gif)
![](data/chem/img/PC1.gif)
![](data/chem/img/FES.gif)
![](data/chem/img/FMN.gif)
![](data/chem/img/3PE.gif)
![](data/chem/img/CDL.gif)
![](data/chem/img/GTP.gif)
![](data/chem/img/NAP.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/EHZ.gif)
#43: Chemical | ChemComp-SF4 / #44: Chemical | #45: Chemical | #46: Chemical | ChemComp-FMN / | #47: Chemical | ChemComp-3PE / #48: Chemical | ChemComp-CDL / #50: Chemical | ChemComp-GTP / | #51: Chemical | ChemComp-NAP / | #52: Chemical | ChemComp-ZN / | #53: Chemical | |
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-Details
Has ligand of interest | N |
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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: Very long-chain specific acyl-CoA dehydrogenase, mitochondrial Type: COMPLEX / Entity ID: #1 / Source: NATURAL | |||||||||||||||||||||||||
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Source (natural) | Organism: ![]() ![]() | |||||||||||||||||||||||||
Buffer solution | pH: 7.14 / Details: pH was corrected at room temperature ~22 C | |||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 3.82 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||||||||||||
Specimen support | Details: The grid was also covalently modified by 48 hour incubation in 5 mM HS-C11-EG6 in ethanol in an anoxic glovebox, and washed thrice in ethanol before air drying. Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: UltrAuFoil | |||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
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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 defocus max: 2900 nm / Nominal defocus min: 1500 nm |
Image recording | Electron dose: 45 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 8793 / Symmetry type: POINT |