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Yorodumi- EMDB-16516: 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 2). | ||||||||||||
Map data | globally sharpened consensus map | ||||||||||||
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Keywords | NADH ubiquinone oxidoreductase / Complex I / OXIDOREDUCTASE | ||||||||||||
| Function / homology | Function and homology informationMitochondrial protein import / mesenchymal stem cell proliferation / reproductive system development / blastocyst hatching / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / RHOG GTPase cycle / Mitochondrial ribosome-associated quality control / Mitochondrial translation termination ...Mitochondrial protein import / mesenchymal stem cell proliferation / reproductive system development / blastocyst hatching / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / RHOG GTPase cycle / Mitochondrial ribosome-associated quality control / Mitochondrial translation termination / Respiratory electron transport / circulatory system development / mesenchymal stem cell differentiation / protein insertion into mitochondrial inner membrane / response to light intensity / Mitochondrial protein degradation / stem cell division / mitochondrial large ribosomal subunit assembly / mitochondrial ATP synthesis coupled electron transport / protein lipoylation / cellular response to oxygen levels / sperm head-tail coupling apparatus / neural precursor cell proliferation / mitochondrial [2Fe-2S] assembly complex / mitochondrial large ribosomal subunit binding / ubiquinone biosynthetic process / respiratory chain complex / gliogenesis / negative regulation of non-canonical NF-kappaB signal transduction / cellular respiration / response to hydroperoxide / cardiac muscle tissue development / positive regulation of mitochondrial membrane potential / oxygen sensor activity / [2Fe-2S] cluster assembly / cellular response to glucocorticoid stimulus / iron-sulfur cluster assembly / NADH:ubiquinone reductase (H+-translocating) / ubiquinone binding / mitochondrial electron transport, NADH to ubiquinone / positive regulation of ATP biosynthetic process / proton motive force-driven mitochondrial ATP synthesis / electron transport coupled proton transport / acyl binding / mitochondrial respiratory chain complex I assembly / oxidoreductase activity, acting on NAD(P)H / NADH dehydrogenase activity / respiratory chain complex I / positive regulation of execution phase of apoptosis / NADH dehydrogenase (ubiquinone) activity / acyl carrier activity / extrinsic apoptotic signaling pathway / cellular response to interferon-beta / quinone binding / cellular response to retinoic acid / ATP synthesis coupled electron transport / multicellular organism growth / neurogenesis / negative regulation of reactive oxygen species biosynthetic process / kidney development / reactive oxygen species metabolic process / cerebellum development / muscle contraction / Neutrophil degranulation / response to hormone / fatty acid metabolic process / ionotropic glutamate receptor binding / acrosomal vesicle / regulation of mitochondrial membrane potential / aerobic respiration / DNA damage response, signal transduction by p53 class mediator / mitochondrion organization / response to hydrogen peroxide / response to nicotine / synaptic membrane / respiratory electron transport chain / response to cocaine / sperm end piece / sperm principal piece / monooxygenase activity / circadian rhythm / mitochondrial intermembrane space / 2 iron, 2 sulfur cluster binding / cellular senescence / mitochondrial membrane / NAD binding / gene expression / in utero embryonic development / positive regulation of protein catabolic process / FMN binding / myelin sheath / sperm midpiece / nervous system development / 4 iron, 4 sulfur cluster binding / protease binding / response to oxidative stress / response to ethanol / response to hypoxia / nuclear body / electron transfer activity Similarity search - Function | ||||||||||||
| Biological species | ![]() | ||||||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.2 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: 2024Title: 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
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Downloads & links
-EMDB archive
| Map data | emd_16516.map.gz | 322.9 MB | EMDB map data format | |
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| Header (meta data) | emd-16516-v30.xml emd-16516.xml | 66.4 KB 66.4 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_16516_fsc.xml | 15.8 KB | Display | FSC data file |
| Images | emd_16516.png | 122.6 KB | ||
| Masks | emd_16516_msk_1.map | 347.6 MB | Mask map | |
| Filedesc metadata | emd-16516.cif.gz | 15.1 KB | ||
| Others | emd_16516_half_map_1.map.gz emd_16516_half_map_2.map.gz | 323 MB 323 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-16516 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-16516 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 8ca3MC ![]() 8c2sC ![]() 8ca1C ![]() 8ca4C ![]() 8ca5C M: atomic model generated by this map C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_16516.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_16516_msk_1.map | ||||||||||||
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| Density Histograms |
-Half map: half map 1
| File | emd_16516_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_16516_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: Ubiquinone-9
+Macromolecule #48: 1,2-Distearoyl-sn-glycerophosphoethanolamine
+Macromolecule #49: CARDIOLIPIN
+Macromolecule #50: DODECYL-BETA-D-MALTOSIDE
+Macromolecule #51: GUANOSINE-5'-TRIPHOSPHATE
+Macromolecule #52: NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
+Macromolecule #53: ZINC ION
+Macromolecule #54: ~{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 |
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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 - Type: GLOW DISCHARGE / 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: 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 |
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Keywords
Authors
United Kingdom, 3 items
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Processing
FIELD EMISSION GUN

