+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-17661 | |||||||||
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Title | ACAD9 homodimer WT | |||||||||
Map data | ACAD9 WT | |||||||||
Sample |
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Keywords | Oxidative phosphorylation (OXPHOS) / Fatty Acid Oxidation (FAO) / Mitochondrial Complex I Assembly Complex (MCIA) / Amyloid-beta / SIGNALING PROTEIN | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 6.0 Å | |||||||||
Authors | McGregor L / Acajjaoui S / Desfosses A / Saidi M / Bacia-Verloop M / Schwarz JJ / Juyoux P / Von Velsen J / Bowler MW / McCarthy A ...McGregor L / Acajjaoui S / Desfosses A / Saidi M / Bacia-Verloop M / Schwarz JJ / Juyoux P / Von Velsen J / Bowler MW / McCarthy A / Kandiah E / Gutsche I / Soler-Lopez M | |||||||||
Funding support | France, 1 items
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Citation | Journal: Nat Commun / Year: 2023 Title: The assembly of the Mitochondrial Complex I Assembly complex uncovers a redox pathway coordination. Authors: Lindsay McGregor / Samira Acajjaoui / Ambroise Desfosses / Melissa Saïdi / Maria Bacia-Verloop / Jennifer J Schwarz / Pauline Juyoux / Jill von Velsen / Matthew W Bowler / Andrew A McCarthy ...Authors: Lindsay McGregor / Samira Acajjaoui / Ambroise Desfosses / Melissa Saïdi / Maria Bacia-Verloop / Jennifer J Schwarz / Pauline Juyoux / Jill von Velsen / Matthew W Bowler / Andrew A McCarthy / Eaazhisai Kandiah / Irina Gutsche / Montserrat Soler-Lopez / Abstract: The Mitochondrial Complex I Assembly (MCIA) complex is essential for the biogenesis of respiratory Complex I (CI), the first enzyme in the respiratory chain, which has been linked to Alzheimer's ...The Mitochondrial Complex I Assembly (MCIA) complex is essential for the biogenesis of respiratory Complex I (CI), the first enzyme in the respiratory chain, which has been linked to Alzheimer's disease (AD) pathogenesis. However, how MCIA facilitates CI assembly, and how it is linked with AD pathogenesis, is poorly understood. Here we report the structural basis of the complex formation between the MCIA subunits ECSIT and ACAD9. ECSIT binding induces a major conformational change in the FAD-binding loop of ACAD9, releasing the FAD cofactor and converting ACAD9 from a fatty acid β-oxidation (FAO) enzyme to a CI assembly factor. We provide evidence that ECSIT phosphorylation downregulates its association with ACAD9 and is reduced in neuronal cells upon exposure to amyloid-β (Aβ) oligomers. These findings advance our understanding of the MCIA complex assembly and suggest a possible role for ECSIT in the reprogramming of bioenergetic pathways linked to Aβ toxicity, a hallmark of AD. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_17661.map.gz | 59.5 MB | EMDB map data format | |
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Header (meta data) | emd-17661-v30.xml emd-17661.xml | 14.3 KB 14.3 KB | Display Display | EMDB header |
Images | emd_17661.png | 34 KB | ||
Filedesc metadata | emd-17661.cif.gz | 5 KB | ||
Others | emd_17661_half_map_1.map.gz emd_17661_half_map_2.map.gz | 59.2 MB 59.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-17661 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-17661 | HTTPS FTP |
-Validation report
Summary document | emd_17661_validation.pdf.gz | 1.2 MB | Display | EMDB validaton report |
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Full document | emd_17661_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | emd_17661_validation.xml.gz | 12.3 KB | Display | |
Data in CIF | emd_17661_validation.cif.gz | 14.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-17661 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-17661 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_17661.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | ACAD9 WT | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.827 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: ACAD9 WT. Half A.
File | emd_17661_half_map_1.map | ||||||||||||
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Annotation | ACAD9 WT. Half A. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: ACAD9 WT. Half B.
File | emd_17661_half_map_2.map | ||||||||||||
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Annotation | ACAD9 WT. Half B. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : ACAD9 WT
Entire | Name: ACAD9 WT |
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Components |
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-Supramolecule #1: ACAD9 WT
Supramolecule | Name: ACAD9 WT / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 120 KDa |
-Macromolecule #1: ACAD9 WT
Macromolecule | Name: ACAD9 WT / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Sequence | String: MAFAKELFLG KIKKKEVFPF PEVSQDELNE INQFLGPVEK FFTEEVDSRK IDQEGKIPDE TLEKLKSLGL FGLQVPEEYG GLGFSNTMYS RLGEIISMDG SITVTLAAHQ AIGLKGIILA GTEEQKAKYL PKLASGEHIA AFCLTEPASG SDAASIRSRA TLSEDKKHYI ...String: MAFAKELFLG KIKKKEVFPF PEVSQDELNE INQFLGPVEK FFTEEVDSRK IDQEGKIPDE TLEKLKSLGL FGLQVPEEYG GLGFSNTMYS RLGEIISMDG SITVTLAAHQ AIGLKGIILA GTEEQKAKYL PKLASGEHIA AFCLTEPASG SDAASIRSRA TLSEDKKHYI LNGSKVWITN GGLANIFTVF AKTEVVDSDG SVKDKITAFI VERDFGGVTN GKPEDKLGIR GSNTCEVHFE NTKIPVENIL GEVGDGFKVA MNILNSGRFS MGSVVAGLLK RLIEMTAEYA CTRKQFNKRL SEFGLIQEKF ALMAQKAYVM ESMTYLTAGM LDQPGFPDCS IEAAMVKVFS SEAAWQCVSE ALQILGGLGY TRDYPYERIL RDTRILLIFE GTNEILRMYI ALTGLQHAGR ILTTRIHELK QAKVSTVMDT VGRRLRDSLG RTVDLGLTGN HGVVHPSLAD SANKFEENTY CFGRTVETLL LRFGKTIMEE QLVLKRVANI LINLYGMTAV LSRASRSIRI GLRNHDHEVL LANTFCVEAY LQNLFSLSQL DKYAPENLDE QIKKVSQQIL EKRAYICAHP LDRTCHHHHH H |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: DARK FIELD / Nominal defocus max: 2.4 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER |
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Final reconstruction | Applied symmetry - Point group: C2 (2 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 6.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 13287 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |