+Open data
-Basic information
Entry | Database: PDB / ID: 8phf | ||||||
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Title | Cryo-EM structure of human ACAD9-S191A | ||||||
Components | Complex I assembly factor ACAD9, mitochondrial | ||||||
Keywords | FLAVOPROTEIN / Oxidative phosphorylation (OXPHOS) / Fatty Acid Oxidation (FAO) / Mitochondrial Complex I Assembly Complex (MCIA) / Amyloid-beta / SIGNALING PROTEIN | ||||||
Function / homology | Function and homology information Oxidoreductases; Acting on the CH-CH group of donors; With a flavin as acceptor / long-chain fatty acyl-CoA dehydrogenase activity / medium-chain fatty acyl-CoA dehydrogenase activity / medium-chain fatty acid metabolic process / long-chain fatty acid metabolic process / Complex I biogenesis / acyl-CoA dehydrogenase activity / mitochondrial respiratory chain complex I assembly / mitochondrial membrane / flavin adenine dinucleotide binding ...Oxidoreductases; Acting on the CH-CH group of donors; With a flavin as acceptor / long-chain fatty acyl-CoA dehydrogenase activity / medium-chain fatty acyl-CoA dehydrogenase activity / medium-chain fatty acid metabolic process / long-chain fatty acid metabolic process / Complex I biogenesis / acyl-CoA dehydrogenase activity / mitochondrial respiratory chain complex I assembly / mitochondrial membrane / flavin adenine dinucleotide binding / mitochondrial inner membrane / dendrite / mitochondrion / nucleus Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.6 Å | ||||||
Authors | McGregor, L. / Acajjaoui, S. / Desfosses, A. / Saidi, M. / Bacia-Verloop, M. / Schwarz, J.J. / Juyoux, P. / Von Velsen, J. / Bowler, M.W. / McCarthy, A. ...McGregor, L. / Acajjaoui, S. / Desfosses, A. / Saidi, M. / Bacia-Verloop, M. / Schwarz, J.J. / Juyoux, P. / Von Velsen, J. / Bowler, M.W. / McCarthy, A. / Kandiah, E. / Gutsche, I. / Soler-Lopez, M. | ||||||
Funding support | France, 1items
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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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8phf.cif.gz | 199.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8phf.ent.gz | 156.9 KB | Display | PDB format |
PDBx/mmJSON format | 8phf.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ph/8phf ftp://data.pdbj.org/pub/pdb/validation_reports/ph/8phf | HTTPS FTP |
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-Related structure data
Related structure data | 17660MC 8pheC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 65842.523 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ACAD9 / Production host: Escherichia coli BL21(DE3) (bacteria) References: UniProt: Q9H845, Oxidoreductases; Acting on the CH-CH group of donors; With a flavin as acceptor #2: Chemical | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: ACAD9 S191A / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Value: 0.120 MDa / Experimental value: YES |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Escherichia coli BL21(DE3) (bacteria) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: DARK FIELD / Nominal defocus max: 2400 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 163409 / Symmetry type: POINT | ||||||||||||||||||||||||
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