[English] 日本語
Yorodumi- EMDB-21684: Cryo-EM structure of SLC40/ferroportin with Fab in the presence o... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-21684 | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of SLC40/ferroportin with Fab in the presence of hepcidin | ||||||||||||
Map data | |||||||||||||
Sample |
| ||||||||||||
Function / homology | Ferroportin-1 / Ferroportin1 (FPN1) / iron ion transmembrane transporter activity / peptide hormone binding / MFS transporter superfamily / lateral plasma membrane / basolateral plasma membrane / metal ion binding / Solute carrier family 40 member Function and homology information | ||||||||||||
Biological species | Carlito syrichta (Philippine tarsier) / mouse (mice) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.4 Å | ||||||||||||
Authors | Shen J / Ren Z / Pan Y / Gao S / Yan N / Zhou M | ||||||||||||
Funding support | United States, 3 items
| ||||||||||||
Citation | Journal: Nat Commun / Year: 2020 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 |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_21684.map.gz | 23.3 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-21684-v30.xml emd-21684.xml | 13.6 KB 13.6 KB | Display Display | EMDB header |
Images | emd_21684.png | 91.2 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-21684 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-21684 | HTTPS FTP |
-Validation report
Summary document | emd_21684_validation.pdf.gz | 387.4 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_21684_full_validation.pdf.gz | 386.9 KB | Display | |
Data in XML | emd_21684_validation.xml.gz | 5.5 KB | Display | |
Data in CIF | emd_21684_validation.cif.gz | 6.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21684 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21684 | HTTPS FTP |
-Related structure data
Related structure data | 6wikMC 6vyhC C: citing same article (ref.) M: atomic model generated by this map |
---|---|
Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_21684.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.07 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-Sample components
-Entire : Cryo-EM map of SLC40/ferroportin with Fab in the presence of hepcidin
Entire | Name: Cryo-EM map of SLC40/ferroportin with Fab in the presence of hepcidin |
---|---|
Components |
|
-Supramolecule #1: Cryo-EM map of SLC40/ferroportin with Fab in the presence of hepcidin
Supramolecule | Name: Cryo-EM map of SLC40/ferroportin with Fab in the presence of hepcidin type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
---|---|
Source (natural) | Organism: Carlito syrichta (Philippine tarsier) |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
-Macromolecule #1: 11F9 Fab light-chain
Macromolecule | Name: 11F9 Fab light-chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: mouse (mice) |
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 #2: 11F9 Fab heavy-chain
Macromolecule | Name: 11F9 Fab heavy-chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: mouse (mice) |
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 #3: Solute carrier family 40 protein
Macromolecule | Name: Solute carrier family 40 protein / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Carlito syrichta (Philippine tarsier) |
Molecular weight | Theoretical: 63.705004 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
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 |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 13 mg/mL |
---|---|
Buffer | pH: 7.5 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 305 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | #0 - Image recording ID: 1 / #0 - Film or detector model: GATAN K2 SUMMIT (4k x 4k) / #0 - Detector mode: SUPER-RESOLUTION / #0 - Average electron dose: 50.0 e/Å2 / #1 - Image recording ID: 2 / #1 - Film or detector model: GATAN K2 SUMMIT (4k x 4k) / #1 - Detector mode: SUPER-RESOLUTION / #1 - Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
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 |
-Image processing
Image recording ID | 1 |
---|---|
Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 214136 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |