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Yorodumi- PDB-8dl7: Cryo-EM structure of human ferroportin/slc40 bound to minihepcidi... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8dl7 | |||||||||||||||
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Title | Cryo-EM structure of human ferroportin/slc40 bound to minihepcidin PR73 in nanodisc | |||||||||||||||
Components |
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Keywords | MEMBRANE PROTEIN / SLC40 / Fpn / ferroportin / iron / transporter / hepcidin / minihepcidin / PR73 / human / nanodisc | |||||||||||||||
Function / homology | Function and homology information spleen trabecula formation / iron ion export across plasma membrane / Defective SLC40A1 causes hemochromatosis 4 (HFE4) (duodenum) / Defective SLC40A1 causes hemochromatosis 4 (HFE4) (macrophages) / Defective CP causes aceruloplasminemia (ACERULOP) / Metal ion SLC transporters / lymphocyte homeostasis / iron ion transmembrane transporter activity / iron ion transmembrane transport / ferrous iron transmembrane transporter activity ...spleen trabecula formation / iron ion export across plasma membrane / Defective SLC40A1 causes hemochromatosis 4 (HFE4) (duodenum) / Defective SLC40A1 causes hemochromatosis 4 (HFE4) (macrophages) / Defective CP causes aceruloplasminemia (ACERULOP) / Metal ion SLC transporters / lymphocyte homeostasis / iron ion transmembrane transporter activity / iron ion transmembrane transport / ferrous iron transmembrane transporter activity / endothelium development / peptide hormone binding / establishment of localization in cell / Iron uptake and transport / multicellular organismal-level iron ion homeostasis / synaptic vesicle / basolateral plasma membrane / intracellular iron ion homeostasis / transcription by RNA polymerase II / negative regulation of apoptotic process / apoptotic process / positive regulation of transcription by RNA polymerase II / nucleoplasm / identical protein binding / membrane / metal ion binding / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) Mus musculus (house mouse) synthetic construct (others) | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.7 Å | |||||||||||||||
Authors | Shen, J. / Wilbon, A.S. / Pan, Y. / Zhou, M. | |||||||||||||||
Funding support | United States, 4items
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Citation | Journal: PLoS Biol / Year: 2023 Title: Structural basis of ferroportin inhibition by minihepcidin PR73. Authors: Azaan Saalim Wilbon / Jiemin Shen / Piotr Ruchala / Ming Zhou / Yaping Pan / Abstract: Ferroportin (Fpn) is the only known iron exporter in humans and is essential for maintaining iron homeostasis. Fpn activity is suppressed by hepcidin, an endogenous peptide hormone, which inhibits ...Ferroportin (Fpn) is the only known iron exporter in humans and is essential for maintaining iron homeostasis. Fpn activity is suppressed by hepcidin, an endogenous peptide hormone, which inhibits iron export and promotes endocytosis of Fpn. Hepcidin deficiency leads to hemochromatosis and iron-loading anemia. Previous studies have shown that small peptides that mimic the first few residues of hepcidin, i.e., minihepcidins, are more potent than hepcidin. However, the mechanism of enhanced inhibition by minihepcidins remains unclear. Here, we report the structure of human ferroportin in complex with a minihepcidin, PR73 that mimics the first 9 residues of hepcidin, at 2.7 Å overall resolution. The structure reveals novel interactions that were not present between Fpn and hepcidin. We validate PR73-Fpn interactions through binding and transport assays. These results provide insights into how minihepcidins increase inhibition potency and will guide future development of Fpn inhibitors. | |||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8dl7.cif.gz | 189.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8dl7.ent.gz | 140.4 KB | Display | PDB format |
PDBx/mmJSON format | 8dl7.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8dl7_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 8dl7_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 8dl7_validation.xml.gz | 33.9 KB | Display | |
Data in CIF | 8dl7_validation.cif.gz | 50.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dl/8dl7 ftp://data.pdbj.org/pub/pdb/validation_reports/dl/8dl7 | HTTPS FTP |
-Related structure data
Related structure data | 27498MC 8dl8C 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
-Antibody , 2 types, 2 molecules CD
#2: Antibody | Mass: 23493.885 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) |
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#3: Antibody | Mass: 25815.039 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) |
-Protein / Protein/peptide , 2 types, 2 molecules AF
#1: Protein | Mass: 63386.621 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SLC40A1, FPN1, IREG1, SLC11A3, MSTP079 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9NP59 |
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#4: Protein/peptide | Type: Peptide-like / Class: Inhibitor / Mass: 1736.198 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) / References: BIRD: PRD_002510 |
-Non-polymers , 2 types, 3 molecules
#5: Chemical | #6: Water | ChemComp-HOH / | |
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-Details
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: Cryo-EM structure of human ferroportin/slc40 bound to minihepcidin PR73 in nanodisc Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 10 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 305 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 50 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 162586 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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