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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 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 / protein insertion into mitochondrial inner membrane / response to light intensity / blastocyst hatching ...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 / protein insertion into mitochondrial inner membrane / response to light intensity / blastocyst hatching / circulatory system development / ubiquinone-6 biosynthetic process / cellular response to oxygen levels / iron-sulfur cluster assembly complex / mitochondrial large ribosomal subunit binding / gliogenesis / neural precursor cell proliferation / [2Fe-2S] cluster assembly / mitochondrial respirasome / NADH dehydrogenase activity / cardiac muscle tissue development / oxygen sensor activity / respiratory chain complex I / cellular respiration / negative regulation of non-canonical NF-kappaB signal transduction / ubiquinone binding / cellular response to glucocorticoid stimulus / positive regulation of mitochondrial membrane potential / acyl binding / response to hydroperoxide / mitochondrial ribosome / electron transport coupled proton transport / iron-sulfur cluster assembly / mitochondrial ATP synthesis coupled electron transport / acyl carrier activity / mitochondrial translation / NADH:ubiquinone reductase (H+-translocating) / positive regulation of ATP biosynthetic process / proton motive force-driven mitochondrial ATP synthesis / mitochondrial respiratory chain complex I / apoptotic mitochondrial changes / mitochondrial respiratory chain complex I assembly / mitochondrial electron transport, NADH to ubiquinone / electron transport chain / NADH dehydrogenase (ubiquinone) activity / quinone binding / ATP synthesis coupled electron transport / cellular response to interferon-beta / negative regulation of intrinsic apoptotic signaling pathway / aerobic respiration / ATP metabolic process / negative regulation of reactive oxygen species biosynthetic process / cellular response to retinoic acid / extrinsic apoptotic signaling pathway / response to organonitrogen compound / ionotropic glutamate receptor binding / respiratory electron transport chain / reactive oxygen species metabolic process / Neutrophil degranulation / cerebellum development / mitochondrion organization / neurogenesis / response to hormone / response to cocaine / fatty acid metabolic process / regulation of mitochondrial membrane potential / response to nicotine / synaptic membrane / muscle contraction / kidney development / apoptotic signaling pathway / mitochondrial membrane / multicellular organism growth / response to hydrogen peroxide / mitochondrial intermembrane space / 2 iron, 2 sulfur cluster binding / negative regulation of cell growth / response to organic cyclic compound / 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 / mitochondrial inner membrane / response to oxidative stress / in utero embryonic development / protease binding / electron transfer activity / response to hypoxia / nuclear body / mitochondrial matrix / structural constituent of ribosome / nuclear speck / response to xenobiotic stimulus / negative regulation of DNA-templated transcription / dendrite / neuronal cell body 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 |
-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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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.9 µm / Nominal defocus min: 1.5 µm |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 45.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |