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Yorodumi- PDB-8ca3: Cryo-EM structure NDUFS4 knockout complex I from Mus musculus hea... -
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-Basic information
Entry | Database: PDB / ID: 8ca3 | ||||||||||||
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Title | Cryo-EM structure NDUFS4 knockout complex I from Mus musculus heart (Class 2). | ||||||||||||
Components |
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Keywords | OXIDOREDUCTASE / NADH ubiquinone oxidoreductase / Complex I | ||||||||||||
Function / homology | Function and homology information reproductive system development / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / Mitochondrial protein import / RHOG GTPase cycle / Respiratory electron transport / protein insertion into mitochondrial inner membrane / blastocyst hatching / circulatory system development ...reproductive system development / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / Mitochondrial protein import / RHOG GTPase cycle / Respiratory electron transport / protein insertion into mitochondrial inner membrane / blastocyst hatching / circulatory system development / Mitochondrial protein degradation / response to light intensity / cellular response to oxygen levels / iron-sulfur cluster assembly complex / ubiquinone-6 biosynthetic process / mitochondrial large ribosomal subunit binding / gliogenesis / cellular response to glucocorticoid stimulus / neural precursor cell proliferation / cardiac muscle tissue development / : / negative regulation of non-canonical NF-kappaB signal transduction / [2Fe-2S] cluster assembly / oxygen sensor activity / positive regulation of mitochondrial membrane potential / response to hydroperoxide / cellular respiration / : / respiratory chain complex I / mitochondrial ribosome / iron-sulfur cluster assembly / mitochondrial translation / ubiquinone binding / positive regulation of ATP biosynthetic process / positive regulation of execution phase of apoptosis / NADH:ubiquinone reductase (H+-translocating) / proton motive force-driven mitochondrial ATP synthesis / NADH dehydrogenase activity / apoptotic mitochondrial changes / : / mitochondrial ATP synthesis coupled electron transport / mitochondrial electron transport, NADH to ubiquinone / mitochondrial respiratory chain complex I assembly / electron transport coupled proton transport / acyl binding / cellular response to interferon-beta / acyl carrier activity / NADH dehydrogenase (ubiquinone) activity / quinone binding / cellular response to retinoic acid / ATP synthesis coupled electron transport / negative regulation of intrinsic apoptotic signaling pathway / negative regulation of reactive oxygen species biosynthetic process / muscle contraction / ATP metabolic process / extrinsic apoptotic signaling pathway / ionotropic glutamate receptor binding / aerobic respiration / response to hormone / Neutrophil degranulation / neurogenesis / respiratory electron transport chain / reactive oxygen species metabolic process / cerebellum development / kidney development / regulation of mitochondrial membrane potential / response to cocaine / mitochondrion organization / synaptic membrane / fatty acid metabolic process / response to nicotine / apoptotic signaling pathway / mitochondrial membrane / electron transport chain / response to hydrogen peroxide / multicellular organism growth / response to organic cyclic compound / negative regulation of cell growth / mitochondrial intermembrane space / 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 / protease binding / in utero embryonic development / response to ethanol / response to oxidative stress / mitochondrial inner membrane / electron transfer activity / nuclear body / response to hypoxia / nuclear speck / mitochondrial matrix / structural constituent of ribosome / response to xenobiotic stimulus / negative regulation of DNA-templated transcription Similarity search - Function | ||||||||||||
Biological species | Mus musculus (house mouse) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||||||||
Authors | Yin, Z. / Bridges, H.R. / Agip, A.N.A. / Hirst, J. | ||||||||||||
Funding support | United Kingdom, 3items
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Citation | Journal: EMBO J / Year: 2024 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: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ca3.cif.gz | 1.6 MB | Display | PDBx/mmCIF format |
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PDB format | pdb8ca3.ent.gz | 1.3 MB | Display | PDB format |
PDBx/mmJSON format | 8ca3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8ca3_validation.pdf.gz | 2.7 MB | Display | wwPDB validaton report |
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Full document | 8ca3_full_validation.pdf.gz | 2.8 MB | Display | |
Data in XML | 8ca3_validation.xml.gz | 208.3 KB | Display | |
Data in CIF | 8ca3_validation.cif.gz | 309.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ca/8ca3 ftp://data.pdbj.org/pub/pdb/validation_reports/ca/8ca3 | HTTPS FTP |
-Related structure data
Related structure data | 16516MC 8c2sC 8ca1C 8ca4C 8ca5C C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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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) Mus musculus (house mouse) 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) Mus musculus (house mouse) 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) Mus musculus (house mouse) 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) Mus musculus (house mouse) 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) Mus musculus (house mouse) 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) Mus musculus (house mouse) 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) Mus musculus (house mouse) 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) Mus musculus (house mouse) 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) Mus musculus (house mouse) 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) Mus musculus (house mouse) 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) Mus musculus (house mouse) 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) Mus musculus (house mouse) / References: UniProt: P52503 |
#29: Protein | Mass: 12675.772 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: Q99LY9 |
-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) Mus musculus (house mouse) 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) Mus musculus (house mouse) 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) Mus musculus (house mouse) / References: UniProt: Q8BK30 |
-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) Mus musculus (house mouse) 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) Mus musculus (house mouse) / References: UniProt: Q9CR21 #23: Protein | | Mass: 15130.416 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: G5E814 |
-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) Mus musculus (house mouse) / References: UniProt: Q99LC3 |
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#16: Protein | Mass: 42588.129 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: Q9DC69 |
#18: Protein | Mass: 10932.675 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: Q9CQ75 |
#20: Protein | Mass: 13380.719 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: Q9CPP6 |
#21: Protein | Mass: 15311.858 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: Q9CQZ5 |
#22: Protein | Mass: 20025.127 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: Q9DCJ5 |
#24: Protein | Mass: 16881.588 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: Q9ERS2 |
#25: Protein | Mass: 8149.524 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: O35683 |
#26: Protein | Mass: 9338.867 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: Q9CQ91 |
#41: Protein | Mass: 12595.592 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: Q9Z1P6 |
-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) Mus musculus (house mouse) / References: UniProt: Q9CQY9 |
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#28: Protein | Mass: 14185.692 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: Q9CQ54 |
-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) Mus musculus (house mouse) / References: UniProt: P0DN34 |
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#31: Protein | Mass: 17463.727 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: O09111 |
#32: Protein | Mass: 21742.197 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: Q9CQH3 |
#33: Protein | Mass: 15450.925 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: Q3UIU2 |
#34: Protein | Mass: 11982.437 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: Q9CPU2 |
#35: Protein | Mass: 11714.240 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: Q9CQZ6 |
#36: Protein | Mass: 21903.828 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: Q9D6J5 |
#37: Protein | Mass: 15105.287 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: Q9CQC7 |
#38: Protein | Mass: 22020.123 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: Q9CQJ8 |
#39: Protein | Mass: 16360.804 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: Q9CR61 |
#40: Protein | Mass: 21054.832 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / References: UniProt: Q9DCS9 |
-Sugars , 1 types, 2 molecules
#50: Sugar |
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-Non-polymers , 11 types, 30 molecules
#43: Chemical | ChemComp-SF4 / #44: Chemical | #45: Chemical | #46: Chemical | ChemComp-FMN / | #47: Chemical | ChemComp-UQ9 / | #48: Chemical | ChemComp-3PE / #49: Chemical | ChemComp-CDL / #51: Chemical | ChemComp-GTP / | #52: Chemical | ChemComp-NDP / | #53: Chemical | ChemComp-ZN / | #54: 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 |
-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: Mus musculus (house mouse) | |||||||||||||||||||||||||
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 |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
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) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 10005 / Symmetry type: POINT |