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- EMDB-27498: Cryo-EM structure of human ferroportin/slc40 bound to minihepcidi... -
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Basic information
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Title | Cryo-EM structure of human ferroportin/slc40 bound to minihepcidin PR73 in nanodisc | |||||||||||||||
![]() | Unsharpened map of human ferroportin/slc40 bound to minihepcidin PR73 | |||||||||||||||
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Function / homology | ![]() 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 / iron ion transmembrane transport / lymphocyte homeostasis / iron ion transmembrane transporter activity / 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 / iron ion transmembrane transport / lymphocyte homeostasis / iron ion transmembrane transporter activity / ferrous iron transmembrane transporter activity / endothelium development / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||||||||
Method | ![]() ![]() | |||||||||||||||
![]() | Shen J / Wilbon AS / Pan Y / Zhou M | |||||||||||||||
Funding support | ![]()
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![]() | ![]() 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
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 15.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.3 KB 18.3 KB | Display Display | ![]() |
Images | ![]() | 81.6 KB | ||
Filedesc metadata | ![]() | 6.9 KB | ||
Others | ![]() ![]() | 28.2 MB 28.2 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8dl7MC ![]() 8dl8C M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Unsharpened map of human ferroportin/slc40 bound to minihepcidin PR73 | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: Half A map of human ferroportin/slc40 bound to minihepcidin PR73
File | emd_27498_half_map_1.map | ||||||||||||
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Annotation | Half_A map of human ferroportin/slc40 bound to minihepcidin PR73 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half B map of human ferroportin/slc40 bound to minihepcidin PR73
File | emd_27498_half_map_2.map | ||||||||||||
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Annotation | Half_B map of human ferroportin/slc40 bound to minihepcidin PR73 | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Cryo-EM structure of human ferroportin/slc40 bound to minihepcidi...
Entire | Name: Cryo-EM structure of human ferroportin/slc40 bound to minihepcidin PR73 in nanodisc |
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Components |
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-Supramolecule #1: Cryo-EM structure of human ferroportin/slc40 bound to minihepcidi...
Supramolecule | Name: Cryo-EM structure of human ferroportin/slc40 bound to minihepcidin PR73 in nanodisc type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Solute carrier family 40 member 1
Macromolecule | Name: Solute carrier family 40 member 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 63.386621 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MTRAGDHNRQ RGCCGSLADY LTSAKFLLYL GHSLSTWGDR MWHFAVSVFL VELYGNSLLL TAVYGLVVAG SVLVLGAIIG DWVDKNARL KVAQTSLVVQ NVSVILCGII LMMVFLHKHE LLTMYHGWVL TSCYILIITI ANIANLASTA TAITIQRDWI V VVAGEDRS ...String: MTRAGDHNRQ RGCCGSLADY LTSAKFLLYL GHSLSTWGDR MWHFAVSVFL VELYGNSLLL TAVYGLVVAG SVLVLGAIIG DWVDKNARL KVAQTSLVVQ NVSVILCGII LMMVFLHKHE LLTMYHGWVL TSCYILIITI ANIANLASTA TAITIQRDWI V VVAGEDRS KLANMNATIR RIDQLTNILA PMAVGQIMTF GSPVIGCGFI SGWNLVSMCV EYVLLWKVYQ KTPALAVKAG LK EEETELK QLNLHKDTEP KPLEGTHLMG VKDSNIHELE HEQEPTCASQ MAEPFRTFRD GWVSYYNQPV FLAGMGLAFL YMT VLGFDC ITTGYAYTQG LSGSILSILM GASAITGIMG TVAFTWLRRK CGLVRTGLIS GLAQLSCLIL CVISVFMPGS PLDL SVSPF EDIRSRFIQG ESITPTKIPE ITTEIYMSNG SNSANIVPET SPESVPIISV SLLFAGVIAA RIGLWSFDLT VTQLL QENV IESERGIING VQNSMNYLLD LLHFIMVILA PNPEAFGLLV LISVSFVAMG HIMYFRFAQN TLGNKLFACG PDAKEV RKE NQANTSVVEN LYFQ UniProtKB: Solute carrier family 40 member 1 |
-Macromolecule #2: 11F9 light-chain
Macromolecule | Name: 11F9 light-chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() ![]() |
Molecular weight | Theoretical: 23.493885 KDa |
Sequence | String: DIVMTQSQKF MSTSVGDRVS ITCKASQNVG TAVAWYQKKP GQSPKLLIYS ASNRYSGVPD RFTGSGSGTD FTLTISNMQS EDLADYFCQ QYGSYPLTFG SGTKLEIKEA EAAPTVSIFP PSSEQLTSGG ASVVCFLNNF YPKDINVKWK IDGSERQNGV L NSWTDQDS ...String: DIVMTQSQKF MSTSVGDRVS ITCKASQNVG TAVAWYQKKP GQSPKLLIYS ASNRYSGVPD RFTGSGSGTD FTLTISNMQS EDLADYFCQ QYGSYPLTFG SGTKLEIKEA EAAPTVSIFP PSSEQLTSGG ASVVCFLNNF YPKDINVKWK IDGSERQNGV L NSWTDQDS KDSTYSMSST LTLTKDEYER HNSYTCEATH KTSTSPIVKS FNRNE |
-Macromolecule #3: 11F9 heavy-chain
Macromolecule | Name: 11F9 heavy-chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() ![]() |
Molecular weight | Theoretical: 25.815039 KDa |
Sequence | String: MKCSWVIFFL MAVVTGVNSE VQLQQSGAEL VRPGALVKLS CKASGFNIKD YYMHWVKERP EQGLEWIGWI DPENGNTIYD PKFQGKASI TADTSSNTAY LQLSSLTSED TAVYYCARKR GYYGPYFDYW GQGTTLTVSS KTTAPSVYPL APVCGDTTGS S VTLGCLVK ...String: MKCSWVIFFL MAVVTGVNSE VQLQQSGAEL VRPGALVKLS CKASGFNIKD YYMHWVKERP EQGLEWIGWI DPENGNTIYD PKFQGKASI TADTSSNTAY LQLSSLTSED TAVYYCARKR GYYGPYFDYW GQGTTLTVSS KTTAPSVYPL APVCGDTTGS S VTLGCLVK GYFPEPVTLT WNSGSLSSGV HTFPAVLQSG LYTLSSSVTV TSSTWPSQSI TCNVAHPASS TKVDKKIEPA |
-Macromolecule #4: Minihepcidin PR73
Macromolecule | Name: Minihepcidin PR73 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: synthetic construct (others) |
Molecular weight | Theoretical: 1.736198 KDa |
Sequence | String: (SQ6)TH(2GX)(EOE)RCR(3FB)(ACA) (SOW)(SQI) |
-Macromolecule #5: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...
Macromolecule | Name: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate type: ligand / ID: 5 / Number of copies: 2 / Formula: POV |
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Molecular weight | Theoretical: 760.076 Da |
Chemical component information | ![]() ChemComp-POV: |
-Macromolecule #6: water
Macromolecule | Name: water / type: ligand / ID: 6 / Number of copies: 1 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ![]() ChemComp-HOH: |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Concentration | 10 mg/mL |
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Buffer | pH: 7.5 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 305 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 50.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: INSILICO MODEL |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 162586 |