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- EMDB-16398: Cryo-EM structure NDUFS4 knockout complex I from Mus musculus hea... -
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Basic information
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Title | Cryo-EM structure NDUFS4 knockout complex I from Mus musculus heart (Class 1). | ||||||||||||
![]() | globally sharpened consensus map | ||||||||||||
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![]() | NADH ubiquinone oxidoreductase / Complex I / OXIDOREDUCTASE | ||||||||||||
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 / mesenchymal stem cell proliferation / reproductive system development ...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 / mesenchymal stem cell proliferation / reproductive system development / Mitochondrial protein degradation / cellular response to oxygen levels / response to light intensity / respiratory chain complex / mesenchymal stem cell differentiation / circulatory system development / mitochondrial [2Fe-2S] assembly complex / iron-sulfur cluster assembly complex / mitochondrial large ribosomal subunit binding / 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 / stem cell division / oxygen sensor activity / response to hydroperoxide / cellular response to glucocorticoid stimulus / iron-sulfur cluster assembly / NADH:ubiquinone reductase (H+-translocating) / positive regulation of ATP biosynthetic process / mitochondrial respiratory chain complex I assembly / NADH dehydrogenase activity / mitochondrial electron transport, NADH to ubiquinone / proton motive force-driven mitochondrial ATP synthesis / positive regulation of execution phase of apoptosis / respiratory chain complex I / NADH dehydrogenase (ubiquinone) activity / quinone binding / cellular response to interferon-beta / : / ATP synthesis coupled electron transport / extrinsic apoptotic signaling pathway / negative regulation of reactive oxygen species biosynthetic process / cellular response to retinoic acid / neurogenesis / Neutrophil degranulation / muscle contraction / cerebellum development / reactive oxygen species metabolic process / aerobic respiration / regulation of mitochondrial membrane potential / respiratory electron transport chain / DNA damage response, signal transduction by p53 class mediator / mitochondrion organization / fatty acid metabolic process / kidney development / response to nicotine / response to cocaine / response to hydrogen peroxide / monooxygenase activity / electron transport chain / mitochondrial membrane / mitochondrial intermembrane space / multicellular organism growth / 2 iron, 2 sulfur cluster binding / circadian rhythm / positive regulation of protein catabolic process / NAD binding / fatty acid biosynthetic process / cellular senescence / FMN binding / nervous system development / myelin sheath / 4 iron, 4 sulfur cluster binding / response to ethanol / gene expression / in utero embryonic development / response to oxidative stress / response to hypoxia / electron transfer activity / mitochondrial inner membrane / nuclear speck / nuclear body / 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 / metal ion binding / nucleus / cytoplasm Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | ||||||||||||
![]() | Yin Z / Bridges HR / Agip ANA / 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. | ||||||||||||
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 323 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 59.5 KB 59.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 15.9 KB | Display | ![]() |
Images | ![]() | 129.3 KB | ||
Masks | ![]() | 347.6 MB | ![]() | |
Filedesc metadata | ![]() | 13.9 KB | ||
Others | ![]() ![]() | 322.1 MB 322.1 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 1.4 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 23.5 KB | Display | |
Data in CIF | ![]() | 31.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8c2sMC ![]() 8ca1C ![]() 8ca3C ![]() 8ca4C ![]() 8ca5C M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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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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Annotation | globally sharpened consensus map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.352 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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Density Histograms |
-Half map: half map 1
File | emd_16398_half_map_1.map | ||||||||||||
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Annotation | half map 1 | ||||||||||||
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Density Histograms |
-Half map: half map 2
File | emd_16398_half_map_2.map | ||||||||||||
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Annotation | half map 2 | ||||||||||||
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Density Histograms |
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Sample components
+Entire : Very long-chain specific acyl-CoA dehydrogenase, mitochondrial
+Supramolecule #1: Very long-chain specific acyl-CoA dehydrogenase, mitochondrial
+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
+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, mi...
+Macromolecule #16: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mit...
+Macromolecule #17: NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial
+Macromolecule #18: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2
+Macromolecule #19: Acyl carrier protein, mitochondrial
+Macromolecule #20: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5
+Macromolecule #21: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6
+Macromolecule #22: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8
+Macromolecule #23: MCG5603
+Macromolecule #24: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13
+Macromolecule #25: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1
+Macromolecule #26: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3
+Macromolecule #27: NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial
+Macromolecule #28: NADH dehydrogenase [ubiquinone] 1 subunit C2
+Macromolecule #29: NADH dehydrogenase [ubiquinone] iron-sulfur protein 5
+Macromolecule #30: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1
+Macromolecule #31: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mit...
+Macromolecule #32: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 5, mito...
+Macromolecule #33: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6
+Macromolecule #34: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mito...
+Macromolecule #35: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3
+Macromolecule #36: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mito...
+Macromolecule #37: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4
+Macromolecule #38: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9
+Macromolecule #39: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7
+Macromolecule #40: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10
+Macromolecule #41: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7
+Macromolecule #42: NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial
+Macromolecule #43: IRON/SULFUR CLUSTER
+Macromolecule #44: 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE
+Macromolecule #45: FE2/S2 (INORGANIC) CLUSTER
+Macromolecule #46: FLAVIN MONONUCLEOTIDE
+Macromolecule #47: 1,2-Distearoyl-sn-glycerophosphoethanolamine
+Macromolecule #48: CARDIOLIPIN
+Macromolecule #49: DODECYL-BETA-D-MALTOSIDE
+Macromolecule #50: GUANOSINE-5'-TRIPHOSPHATE
+Macromolecule #51: NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
+Macromolecule #52: ZINC ION
+Macromolecule #53: ~{S}-[2-[3-[[(2~{R})-3,3-dimethyl-2-oxidanyl-4-phosphonooxy-butan...
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 3.82 mg/mL | |||||||||||||||
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Buffer | pH: 7.14 Component:
Details: pH was corrected at room temperature ~22 C | |||||||||||||||
Grid | Model: UltrAuFoil / Material: GOLD / Mesh: 300 / Support film - Material: GOLD / Support film - topology: HOLEY / Pretreatment - Time: 90 sec. / Pretreatment - Atmosphere: AIR 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. | |||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 45.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.9 µm / Nominal defocus min: 1.5 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |