+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-16515 | ||||||||||||
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Title | Cryo-EM structure of the ACADVL dimer from Mus musculus. | ||||||||||||
Map data | globally sharpened map (locally refined). | ||||||||||||
Sample |
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Keywords | NADH ubiquinone oxidoreductase / Complex I / OXIDOREDUCTASE | ||||||||||||
Function / homology | Function and homology information Beta oxidation of palmitoyl-CoA to myristoyl-CoA / very-long-chain acyl-CoA dehydrogenase / very-long-chain fatty acyl-CoA dehydrogenase activity / negative regulation of fatty acid oxidation / long-chain fatty acyl-CoA dehydrogenase activity / fatty acid beta-oxidation using acyl-CoA dehydrogenase / acyl-CoA dehydrogenase activity / fatty-acyl-CoA binding / fatty acid catabolic process / negative regulation of fatty acid biosynthetic process ...Beta oxidation of palmitoyl-CoA to myristoyl-CoA / very-long-chain acyl-CoA dehydrogenase / very-long-chain fatty acyl-CoA dehydrogenase activity / negative regulation of fatty acid oxidation / long-chain fatty acyl-CoA dehydrogenase activity / fatty acid beta-oxidation using acyl-CoA dehydrogenase / acyl-CoA dehydrogenase activity / fatty-acyl-CoA binding / fatty acid catabolic process / negative regulation of fatty acid biosynthetic process / regulation of cholesterol metabolic process / temperature homeostasis / fatty acid beta-oxidation / mitochondrial nucleoid / epithelial cell differentiation / response to cold / flavin adenine dinucleotide binding / mitochondrial inner membrane / nucleolus / mitochondrion / nucleoplasm / identical protein binding Similarity search - Function | ||||||||||||
Biological species | Mus musculus (house mouse) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.3 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_16515.map.gz | 321.8 MB | EMDB map data format | |
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Header (meta data) | emd-16515-v30.xml emd-16515.xml | 16.9 KB 16.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_16515_fsc.xml | 15.9 KB | Display | FSC data file |
Images | emd_16515.png | 94.7 KB | ||
Masks | emd_16515_msk_1.map | 347.6 MB | Mask map | |
Filedesc metadata | emd-16515.cif.gz | 5.8 KB | ||
Others | emd_16515_half_map_1.map.gz emd_16515_half_map_2.map.gz | 321.9 MB 321.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-16515 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-16515 | HTTPS FTP |
-Validation report
Summary document | emd_16515_validation.pdf.gz | 1.5 MB | Display | EMDB validaton report |
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Full document | emd_16515_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | emd_16515_validation.xml.gz | 23.8 KB | Display | |
Data in CIF | emd_16515_validation.cif.gz | 31.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-16515 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-16515 | HTTPS FTP |
-Related structure data
Related structure data | 8ca1MC 8c2sC 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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-Map
File | Download / File: emd_16515.map.gz / Format: CCP4 / Size: 347.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | globally sharpened map (locally refined). | ||||||||||||||||||||||||||||||||||||
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_16515_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: half map 1
File | emd_16515_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_16515_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
Entire | Name: Very long-chain specific acyl-CoA dehydrogenase, mitochondrial |
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Components |
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-Supramolecule #1: Very long-chain specific acyl-CoA dehydrogenase, mitochondrial
Supramolecule | Name: Very long-chain specific acyl-CoA dehydrogenase, mitochondrial type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Mus musculus (house mouse) |
-Macromolecule #1: Very long-chain specific acyl-CoA dehydrogenase, mitochondrial
Macromolecule | Name: Very long-chain specific acyl-CoA dehydrogenase, mitochondrial type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: very-long-chain acyl-CoA dehydrogenase |
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Source (natural) | Organism: Mus musculus (house mouse) / Organ: heart |
Molecular weight | Theoretical: 70.959375 KDa |
Sequence | String: MQSARMTPSV GRQLLRLGAR SSRSTTVLQG QPRPISAQRL YAREATQAVL DKPETLSSDA STREKPARAE SKSFAVGMFK GQLTIDQVF PYPSVLSEEQ AQFLKELVGP VARFFEEVND PAKNDALEKV EDDTLQGLKE LGAFGLQVPS ELGGLGLSNT Q YARLAEIV ...String: MQSARMTPSV GRQLLRLGAR SSRSTTVLQG QPRPISAQRL YAREATQAVL DKPETLSSDA STREKPARAE SKSFAVGMFK GQLTIDQVF PYPSVLSEEQ AQFLKELVGP VARFFEEVND PAKNDALEKV EDDTLQGLKE LGAFGLQVPS ELGGLGLSNT Q YARLAEIV GMHDLGVSVT LGAHQSIGFK GILLYGTKAQ REKYLPRVAS GQALAAFCLT EPSSGSDVAS IRSSAIPSPC GK YYTLNGS KIWISNGGLA DIFTVFAKTP IKDAATGAVK EKITAFVVER SFGGVTHGLP EKKMGIKASN TSEVYFDGVK VPS ENVLGE VGDGFKVAVN ILNNGRFGMA ATLAGTMKSL IAKAVDHATN RTQFGDKIHN FGVIQEKLAR MAILQYVTES MAYM LSANM DQGFKDFQIE AAISKIFCSE AAWKVADECI QIMGGMGFMK EPGVERVLRD IRIFRIFEGA NDILRLFVAL QGCMD KGKE LTGLGNALKN PFGNVGLLMG EAGKQLRRRT GIGSGLSLSG IVHPELSRSG ELAVQALDQF ATVVEAKLVK HKKGIV NEQ FLLQRLADGA IDLYAMVVVL SRASRSLSEG YPTAQHEKML CDSWCIEAAT RIRENMASLQ SSPQHQELFR NFRSISK AM VENGGLVTGN PLGI UniProtKB: Very long-chain specific acyl-CoA dehydrogenase, mitochondrial |
-Macromolecule #2: FLAVIN-ADENINE DINUCLEOTIDE
Macromolecule | Name: FLAVIN-ADENINE DINUCLEOTIDE / type: ligand / ID: 2 / Number of copies: 2 / Formula: FAD |
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Molecular weight | Theoretical: 785.55 Da |
Chemical component information | ChemComp-FAD: |
-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 - Type: GLOW DISCHARGE / Pretreatment - Time: 90 sec. / Pretreatment - Atmosphere: AIR | |||||||||||||||
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 |