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Yorodumi- EMDB-16398: Cryo-EM structure NDUFS4 knockout complex I from Mus musculus hea... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-16398 | ||||||||||||
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Title | Cryo-EM structure NDUFS4 knockout complex I from Mus musculus heart (Class 1). | ||||||||||||
Map data | globally sharpened consensus map | ||||||||||||
Sample |
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Keywords | NADH ubiquinone oxidoreductase / Complex I / OXIDOREDUCTASE | ||||||||||||
Function / homology | Function and homology information Protein lipoylation / reproductive system development / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / Mitochondrial protein import / RHOG GTPase cycle / Respiratory electron transport / protein insertion into mitochondrial inner membrane / circulatory system development / blastocyst hatching ...Protein lipoylation / reproductive system development / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / Mitochondrial protein import / RHOG GTPase cycle / Respiratory electron transport / protein insertion into mitochondrial inner membrane / circulatory system development / blastocyst hatching / 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 / neural precursor cell proliferation / cardiac muscle tissue development / : / negative regulation of non-canonical NF-kappaB signal transduction / [2Fe-2S] cluster assembly / oxygen sensor activity / cellular response to glucocorticoid stimulus / response to hydroperoxide / positive regulation of mitochondrial membrane potential / cellular respiration / respiratory chain complex I / iron-sulfur cluster assembly / mitochondrial ribosome / mitochondrial translation / positive regulation of ATP biosynthetic process / positive regulation of execution phase of apoptosis / NADH:ubiquinone reductase (H+-translocating) / : / ubiquinone binding / NADH dehydrogenase activity / apoptotic mitochondrial changes / : / mitochondrial ATP synthesis coupled electron transport / mitochondrial electron transport, NADH to ubiquinone / mitochondrial respiratory chain complex I assembly / proton motive force-driven mitochondrial ATP synthesis / electron transport coupled proton transport / acyl binding / cellular response to interferon-beta / acyl carrier activity / NADH dehydrogenase (ubiquinone) activity / quinone binding / ATP synthesis coupled electron transport / cellular response to retinoic acid / negative regulation of intrinsic apoptotic signaling pathway / muscle contraction / negative regulation of reactive oxygen species biosynthetic process / ATP metabolic process / extrinsic apoptotic signaling pathway / aerobic respiration / ionotropic glutamate receptor binding / response to hormone / Neutrophil degranulation / respiratory electron transport chain / reactive oxygen species metabolic process / neurogenesis / cerebellum development / regulation of mitochondrial membrane potential / kidney development / mitochondrion organization / response to cocaine / fatty acid metabolic process / synaptic membrane / mitochondrial membrane / apoptotic signaling pathway / electron transport chain / response to nicotine / 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 / response to ethanol / in utero embryonic development / response to oxidative stress / mitochondrial inner membrane / electron transfer activity / response to hypoxia / nuclear body / nuclear speck / structural constituent of ribosome / mitochondrial matrix / response to xenobiotic stimulus / negative regulation of DNA-templated transcription Similarity search - Function | ||||||||||||
Biological species | Mus musculus (house mouse) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | ||||||||||||
Authors | Yin Z / Bridges HR / Agip ANA / Hirst J | ||||||||||||
Funding support | United Kingdom, 3 items
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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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_16398.map.gz | 323 MB | EMDB map data format | |
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Header (meta data) | emd-16398-v30.xml emd-16398.xml | 59.5 KB 59.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_16398_fsc.xml | 15.9 KB | Display | FSC data file |
Images | emd_16398.png | 129.3 KB | ||
Masks | emd_16398_msk_1.map | 347.6 MB | Mask map | |
Filedesc metadata | emd-16398.cif.gz | 13.9 KB | ||
Others | emd_16398_half_map_1.map.gz emd_16398_half_map_2.map.gz | 322.1 MB 322.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-16398 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-16398 | HTTPS FTP |
-Validation report
Summary document | emd_16398_validation.pdf.gz | 1.4 MB | Display | EMDB validaton report |
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Full document | emd_16398_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | emd_16398_validation.xml.gz | 23.5 KB | Display | |
Data in CIF | emd_16398_validation.cif.gz | 31.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-16398 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-16398 | HTTPS FTP |
-Related structure data
Related structure data | 8c2sMC 8ca1C 8ca3C 8ca4C 8ca5C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_16398.map.gz / Format: CCP4 / Size: 347.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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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
File | emd_16398_msk_1.map | ||||||||||||
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Projections & Slices |
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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 | ||||||||||||
Projections & Slices |
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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 | ||||||||||||
Projections & Slices |
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Density Histograms |
-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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Processing | single particle reconstruction |
Aggregation state | particle |
-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 |
-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: FIELD EMISSION GUN |
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 |