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- PDB-8ca5: Cryo-EM structure NDUFS4 knockout complex I from Mus musculus hea... -
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Basic information
Entry | Database: PDB / ID: 8ca5 | ||||||||||||
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Title | Cryo-EM structure NDUFS4 knockout complex I from Mus musculus heart (Class 3). | ||||||||||||
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![]() | OXIDOREDUCTASE / NADH ubiquinone oxidoreductase / Complex I | ||||||||||||
Function / homology | ![]() Mitochondrial protein import / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / RHOG GTPase cycle / Respiratory electron transport / protein insertion into mitochondrial inner membrane / blastocyst hatching / Mitochondrial protein degradation / response to light intensity ...Mitochondrial protein import / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / RHOG GTPase cycle / Respiratory electron transport / protein insertion into mitochondrial inner membrane / blastocyst hatching / Mitochondrial protein degradation / response to light intensity / cellular response to oxygen levels / respiratory chain complex / mitochondrial [2Fe-2S] assembly complex / iron-sulfur cluster assembly complex / mitochondrial large ribosomal subunit binding / negative regulation of insulin secretion involved in cellular response to glucose stimulus / gliogenesis / negative regulation of non-canonical NF-kappaB signal transduction / cardiac muscle tissue development / neural precursor cell proliferation / [2Fe-2S] cluster assembly / positive regulation of mitochondrial membrane potential / cellular response to glucocorticoid stimulus / oxygen sensor activity / response to hydroperoxide / iron-sulfur cluster assembly / positive regulation of ATP biosynthetic process / NADH:ubiquinone reductase (H+-translocating) / positive regulation of execution phase of apoptosis / NADH dehydrogenase activity / mitochondrial electron transport, NADH to ubiquinone / mitochondrial respiratory chain complex I assembly / proton motive force-driven mitochondrial ATP synthesis / respiratory chain complex I / NADH dehydrogenase (ubiquinone) activity / cellular response to interferon-beta / quinone binding / ATP synthesis coupled electron transport / cellular response to retinoic acid / negative regulation of reactive oxygen species biosynthetic process / extrinsic apoptotic signaling pathway / Neutrophil degranulation / cerebellum development / reactive oxygen species metabolic process / aerobic respiration / respiratory electron transport chain / neurogenesis / response to nicotine / electron transport chain / response to cocaine / mitochondrial membrane / : / response to hydrogen peroxide / mitochondrial intermembrane space / 2 iron, 2 sulfur cluster binding / circadian rhythm / positive regulation of protein catabolic process / NAD binding / fatty acid biosynthetic process / FMN binding / myelin sheath / nervous system development / 4 iron, 4 sulfur cluster binding / response to ethanol / in utero embryonic development / response to oxidative stress / electron transfer activity / response to hypoxia / mitochondrial inner membrane / nuclear body / nuclear speck / mitochondrial matrix / response to xenobiotic stimulus / negative regulation of DNA-templated transcription / neuronal cell body / dendrite / ubiquitin protein ligase binding / protein-containing complex binding / mitochondrion / nucleoplasm / ATP binding / nucleus / membrane / metal ion binding / cytosol / cytoplasm 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 | ![]() | 3.2 MB | Display | ![]() |
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Full document | ![]() | 3.3 MB | Display | |
Data in XML | ![]() | 229.8 KB | Display | |
Data in CIF | ![]() | 334.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 16518MC ![]() 8c2sC ![]() 8ca1C ![]() 8ca3C ![]() 8ca4C C: citing same article ( M: map data used to model this data |
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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
-Protein , 4 types, 5 molecules tGTUY
#1: Protein | Mass: 19658.855 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() | ||
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#8: 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) | ||
#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-ubiquinone oxidoreductase chain ... , 7 types, 7 molecules AHJKLMN
#2: 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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#9: 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) |
#11: 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) |
#12: 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) |
#13: 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) |
#14: 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) |
#15: 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 ... , 5 types, 5 molecules BCDIe
#3: 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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#4: 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) |
#5: 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) |
#10: 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) |
#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
#6: 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) |
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#7: 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) ![]() ![]() |
-NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit ... , 10 types, 10 molecules OPSVWXZabr
#16: Protein | Mass: 40657.375 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#17: 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: 15540.085 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 
#50: Sugar |
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-Non-polymers , 10 types, 29 molecules 


















#43: Chemical | ChemComp-SF4 / #44: Chemical | #45: Chemical | ChemComp-3PE / #46: Chemical | #47: Chemical | ChemComp-FMN / | #48: Chemical | ChemComp-UQ9 / | #49: Chemical | ChemComp-CDL / #51: Chemical | ChemComp-GTP / | #52: Chemical | ChemComp-NDP / | #53: Chemical | |
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-Details
Has ligand of interest | N |
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Has protein modification | Y |
-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-#42 / 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 | 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: 10005 / Symmetry type: POINT |