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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-21460 | ||||||||||||
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Title | Cryo-EM structure of SLC40/ferroportin in complex with Fab | ||||||||||||
![]() | structure of SLC40/ferroportin in complex with Fab | ||||||||||||
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Function / homology | ![]() iron ion transmembrane transporter activity / peptide hormone binding / basolateral plasma membrane / intracellular iron ion homeostasis / nucleoplasm / cytosol Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | ||||||||||||
![]() | Shen J / Ren Z / Pan Y / Gao S / Yan N / Zhou M | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis of ion transport and inhibition in ferroportin. Authors: Yaping Pan / Zhenning Ren / Shuai Gao / Jiemin Shen / Lie Wang / Zhichun Xu / Ye Yu / Preetham Bachina / Hanzhi Zhang / Xiao Fan / Arthur Laganowsky / Nieng Yan / Ming Zhou / ![]() Abstract: Ferroportin is an iron exporter essential for releasing cellular iron into circulation. Ferroportin is inhibited by a peptide hormone, hepcidin. In humans, mutations in ferroportin lead to ...Ferroportin is an iron exporter essential for releasing cellular iron into circulation. Ferroportin is inhibited by a peptide hormone, hepcidin. In humans, mutations in ferroportin lead to ferroportin diseases that are often associated with accumulation of iron in macrophages and symptoms of iron deficiency anemia. Here we present the structures of the ferroportin from the primate Philippine tarsier (TsFpn) in the presence and absence of hepcidin solved by cryo-electron microscopy. TsFpn is composed of two domains resembling a clamshell and the structure defines two metal ion binding sites, one in each domain. Both structures are in an outward-facing conformation, and hepcidin binds between the two domains and reaches one of the ion binding sites. Functional studies show that TsFpn is an electroneutral H/Fe antiporter so that transport of each Fe is coupled to transport of two H in the opposite direction. Perturbing either of the ion binding sites compromises the coupled transport of H and Fe. These results establish the structural basis of metal ion binding, transport and inhibition in ferroportin and provide a blueprint for targeting ferroportin in pharmacological intervention of ferroportin diseases. | ||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 28.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.1 KB 14.1 KB | Display Display | ![]() |
Images | ![]() | 102.3 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6vyhMC ![]() 6wikC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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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 | structure of SLC40/ferroportin in complex with Fab | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.114 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Cryo-EM map of SLC40/ferroportin in complex with Fab
Entire | Name: Cryo-EM map of SLC40/ferroportin in complex with Fab |
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Components |
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-Supramolecule #1: Cryo-EM map of SLC40/ferroportin in complex with Fab
Supramolecule | Name: Cryo-EM map of SLC40/ferroportin in complex with Fab / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: Solute carrier family 40 protein
Macromolecule | Name: Solute carrier family 40 protein / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 63.705004 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MSRAREQERQ GGCCRSLANY LTSAKFLLYL GHSLSTWGDR MWHFAVSVFL VELYGNSLLL TAVYGLVVAG SVLVLGAIIG DWVDKNARL KVAQTSLVIQ NVSVILCGII LMMVFLHKDE LLTMYHGWVL TSCYILIITI ANIANLASTA TAITIQRDWI V VVAGEDRS ...String: MSRAREQERQ GGCCRSLANY LTSAKFLLYL GHSLSTWGDR MWHFAVSVFL VELYGNSLLL TAVYGLVVAG SVLVLGAIIG DWVDKNARL KVAQTSLVIQ NVSVILCGII LMMVFLHKDE LLTMYHGWVL TSCYILIITI ANIANLASTA TAITIQRDWI V VVAGEDRS KLANMNATVR RIDQLTNILA PMAVGQIMTY GSPVIGCGFI SGWNLVSMCV EYFLLWKVYQ KTPALAVKAA LK VEETELK QLNLHKDTEP KPLEGTHLMG EKDPNIHELE HEQEPTCASQ MAEPFRTFRD GWVSYYNQPI FLAGMGLAFL YMT VLGFDC ITTGYAYTQG LSGSVLSILM GASAITGIMG TVAFTWLRRK CGLVRTGLIS GWAQISCLIL CVISVFMPGS PLDL SVSPF EDIRSRFIQE ELITPTKIPE TIITTEMHIS NGSDLHIAPE ASPQSVPIIS VSLLFAGVIA ARIGLWSFDL TVTQL LQEN VIESERGIIN GVQNSMNYLL DLLHFIMVIL APNPEAFGLL VLISVSFVVM GHIMYFRFAQ KTLGNQLFVC GPDAKE VTN ENQSNTSVVE NLYQ |
-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: COBALT (II) ION
Macromolecule | Name: COBALT (II) ION / type: ligand / ID: 4 / Number of copies: 2 / Formula: CO |
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Molecular weight | Theoretical: 58.933 Da |
-Macromolecule #5: water
Macromolecule | Name: water / type: ligand / ID: 5 / 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 | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 13 mg/mL |
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Buffer | pH: 7.5 |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE |
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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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 215752 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |