[English] 日本語
Yorodumi- PDB-6wik: Cryo-EM structure of SLC40/ferroportin with Fab in the presence o... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6wik | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of SLC40/ferroportin with Fab in the presence of hepcidin | ||||||||||||
Components |
| ||||||||||||
Keywords | MEMBRANE PROTEIN / SLC40 / Fpn / ferroportin / iron transporter / hepcidin | ||||||||||||
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) Mus musculus (house mouse) | ||||||||||||
Method | ELECTRON MICROSCOPY / 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, 3items
| ||||||||||||
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 | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6wik.cif.gz | 153.1 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb6wik.ent.gz | 116.2 KB | Display | PDB format |
PDBx/mmJSON format | 6wik.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6wik_validation.pdf.gz | 713.5 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 6wik_full_validation.pdf.gz | 745.4 KB | Display | |
Data in XML | 6wik_validation.xml.gz | 32 KB | Display | |
Data in CIF | 6wik_validation.cif.gz | 47.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wi/6wik ftp://data.pdbj.org/pub/pdb/validation_reports/wi/6wik | HTTPS FTP |
-Related structure data
Related structure data | 21684MC 6vyhC C: citing same article (ref.) M: map data used to model this data |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
#1: Antibody | Mass: 23493.885 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) |
---|---|
#2: Antibody | Mass: 25815.039 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) |
#3: Protein | Mass: 63705.004 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Carlito syrichta (Philippine tarsier) / Gene: SLC40A1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: A0A1U7U6F1 |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Cryo-EM map of SLC40/ferroportin with Fab in the presence of hepcidin Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
---|---|
Molecular weight | Experimental value: NO |
Source (natural) | Organism: Carlito syrichta (Philippine tarsier) |
Source (recombinant) | Organism: Trichoplusia ni (cabbage looper) |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 13 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 | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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: 1200 nm | |||||||||||||||
Image recording |
|
-Processing
Software | Name: PHENIX / Version: 1.18rc5_3822: / Classification: refinement | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 214136 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
|