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Yorodumi- PDB-8qu9: Structure of the NCOA4 (Nuclear Receptor Coactivator 4)-FTH1 (H-F... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8qu9 | |||||||||
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Title | Structure of the NCOA4 (Nuclear Receptor Coactivator 4)-FTH1 (H-Ferritin) complex | |||||||||
Components |
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Keywords | METAL TRANSPORT / Ferritinophagy / Iron homeostasis / NCOA4 / Ferritin heavy chain | |||||||||
Function / homology | Function and homology information iron ion sequestering activity / : / autolysosome / Scavenging by Class A Receptors / Golgi Associated Vesicle Biogenesis / ferroxidase / intracellular sequestering of iron ion / ferroxidase activity / negative regulation of fibroblast proliferation / ferric iron binding ...iron ion sequestering activity / : / autolysosome / Scavenging by Class A Receptors / Golgi Associated Vesicle Biogenesis / ferroxidase / intracellular sequestering of iron ion / ferroxidase activity / negative regulation of fibroblast proliferation / ferric iron binding / Iron uptake and transport / ferrous iron binding / tertiary granule lumen / iron ion transport / intracellular iron ion homeostasis / ficolin-1-rich granule lumen / immune response / iron ion binding / negative regulation of cell population proliferation / Neutrophil degranulation / extracellular exosome / extracellular region / membrane / identical protein binding / nucleus / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.88 Å | |||||||||
Authors | Hoelzgen, F. / Klukin, E. / Zalk, R. / Shahar, A. / Cohen-Schwartz, S. / Frank, G.A. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Nat Commun / Year: 2024 Title: Structural basis for the intracellular regulation of ferritin degradation. Authors: Fabian Hoelzgen / Thuy T P Nguyen / Elina Klukin / Mohamed Boumaiza / Ayush K Srivastava / Elizabeth Y Kim / Ran Zalk / Anat Shahar / Sagit Cohen-Schwartz / Esther G Meyron-Holtz / Fadi Bou- ...Authors: Fabian Hoelzgen / Thuy T P Nguyen / Elina Klukin / Mohamed Boumaiza / Ayush K Srivastava / Elizabeth Y Kim / Ran Zalk / Anat Shahar / Sagit Cohen-Schwartz / Esther G Meyron-Holtz / Fadi Bou-Abdallah / Joseph D Mancias / Gabriel A Frank / Abstract: The interaction between nuclear receptor coactivator 4 (NCOA4) and the iron storage protein ferritin is a crucial component of cellular iron homeostasis. The binding of NCOA4 to the FTH1 subunits of ...The interaction between nuclear receptor coactivator 4 (NCOA4) and the iron storage protein ferritin is a crucial component of cellular iron homeostasis. The binding of NCOA4 to the FTH1 subunits of ferritin initiates ferritinophagy-a ferritin-specific autophagic pathway leading to the release of the iron stored inside ferritin. The dysregulation of NCOA4 is associated with several diseases, including neurodegenerative disorders and cancer, highlighting the NCOA4-ferritin interface as a prime target for drug development. Here, we present the cryo-EM structure of the NCOA4-FTH1 interface, resolving 16 amino acids of NCOA4 that are crucial for the interaction. The characterization of mutants, designed to modulate the NCOA4-FTH1 interaction, is used to validate the significance of the different features of the binding site. Our results explain the role of the large solvent-exposed hydrophobic patch found on the surface of FTH1 and pave the way for the rational development of ferritinophagy modulators. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8qu9.cif.gz | 50.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8qu9.ent.gz | 35.3 KB | Display | PDB format |
PDBx/mmJSON format | 8qu9.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qu/8qu9 ftp://data.pdbj.org/pub/pdb/validation_reports/qu/8qu9 | HTTPS FTP |
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-Related structure data
Related structure data | 18658MC M: map data used to model this data C: citing same article (ref.) |
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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: 20764.098 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FTH1 / Production host: Escherichia coli (E. coli) / References: UniProt: P02794 | ||||
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#2: Protein/peptide | Mass: 1877.122 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) | ||||
#3: Chemical | #4: Water | ChemComp-HOH / | Has ligand of interest | Y | |
-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: FTH1 NCOA4 complex / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Escherichia coli (E. coli) |
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
Microscopy | Model: TFS GLACIOS |
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Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / Nominal magnification: 130000 X / Nominal defocus max: 2000 nm / Nominal defocus min: 500 nm |
Specimen holder | Cryogen: NITROGEN |
Image recording | Electron dose: 30 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 2.88 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 49794 / Symmetry type: POINT |