[English] 日本語
Yorodumi
- EMDB-21539: Structure of apo human ferroportin in lipid nanodisc -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-21539
TitleStructure of apo human ferroportin in lipid nanodisc
Map dataapo human ferroportin in lipid nanodisc
Sample
  • Complex: Ferroportin-Fab45D8 complex
    • Complex: Ferroportin
      • Protein or peptide: Solute carrier family 40 member 1
    • Complex: Fab45D8
      • Protein or peptide: Fab45D8 Heavy Chain
      • Protein or peptide: Fab45D8 Light Chain
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 / 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 / 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 / apoptotic process / negative regulation of apoptotic process / positive regulation of transcription by RNA polymerase II / nucleoplasm / membrane / identical protein binding / metal ion binding / plasma membrane / cytosol / cytoplasm
Similarity search - Function
Ferroportin-1 / Ferroportin1 (FPN1) / MFS transporter superfamily
Similarity search - Domain/homology
Solute carrier family 40 member 1
Similarity search - Component
Biological speciesHomo sapiens (human) / Mus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsBillesboelle CB / Azumaya CM / Gonen S / Powers A / Kretsch RC / Schneider S / Arvedson T / Dror RO / Cheng Y / Manglik A
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)1DP5OD023048 United States
CitationJournal: Nature / Year: 2020
Title: Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms.
Authors: Christian B Billesbølle / Caleigh M Azumaya / Rachael C Kretsch / Alexander S Powers / Shane Gonen / Simon Schneider / Tara Arvedson / Ron O Dror / Yifan Cheng / Aashish Manglik /
Abstract: The serum level of iron in humans is tightly controlled by the action of the hormone hepcidin on the iron efflux transporter ferroportin. Hepcidin regulates iron absorption and recycling by inducing ...The serum level of iron in humans is tightly controlled by the action of the hormone hepcidin on the iron efflux transporter ferroportin. Hepcidin regulates iron absorption and recycling by inducing the internalization and degradation of ferroportin. Aberrant ferroportin activity can lead to diseases of iron overload, such as haemochromatosis, or iron limitation anaemias. Here we determine cryogenic electron microscopy structures of ferroportin in lipid nanodiscs, both in the apo state and in complex with hepcidin and the iron mimetic cobalt. These structures and accompanying molecular dynamics simulations identify two metal-binding sites within the N and C domains of ferroportin. Hepcidin binds ferroportin in an outward-open conformation and completely occludes the iron efflux pathway to inhibit transport. The carboxy terminus of hepcidin directly contacts the divalent metal in the ferroportin C domain. Hepcidin binding to ferroportin is coupled to iron binding, with an 80-fold increase in hepcidin affinity in the presence of iron. These results suggest a model for hepcidin regulation of ferroportin, in which only ferroportin molecules loaded with iron are targeted for degradation. More broadly, our structural and functional insights may enable more targeted manipulation of the hepcidin-ferroportin axis in disorders of iron homeostasis.
History
DepositionMar 11, 2020-
Header (metadata) releaseApr 8, 2020-
Map releaseSep 9, 2020-
UpdateNov 11, 2020-
Current statusNov 11, 2020Processing site: RCSB / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 4
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by height
  • Surface level: 4
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-6w4s
  • Surface level: 4
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_21539.png

Downloads & links

-
Map

FileDownload / File: emd_21539.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationapo human ferroportin in lipid nanodisc
Voxel sizeX=Y=Z: 0.8488 Å
Density
Contour LevelBy AUTHOR: 4 / Movie #1: 4
Minimum - Maximum-19.696297 - 32.11755
Average (Standard dev.)-0.041166794 (±0.7190685)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 254.64 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z0.84880.84880.8488
M x/y/z300300300
origin x/y/z0.0000.0000.000
length x/y/z254.640254.640254.640
α/β/γ90.00090.00090.000
start NX/NY/NZ000
NX/NY/NZ500500500
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS300300300
D min/max/mean-19.69632.118-0.041

-
Supplemental data

-
Sample components

-
Entire : Ferroportin-Fab45D8 complex

EntireName: Ferroportin-Fab45D8 complex
Components
  • Complex: Ferroportin-Fab45D8 complex
    • Complex: Ferroportin
      • Protein or peptide: Solute carrier family 40 member 1
    • Complex: Fab45D8
      • Protein or peptide: Fab45D8 Heavy Chain
      • Protein or peptide: Fab45D8 Light Chain

-
Supramolecule #1: Ferroportin-Fab45D8 complex

SupramoleculeName: Ferroportin-Fab45D8 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all

-
Supramolecule #2: Ferroportin

SupramoleculeName: Ferroportin / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)

-
Supramolecule #3: Fab45D8

SupramoleculeName: Fab45D8 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3
Source (natural)Organism: Mus musculus (house mouse)
Recombinant expressionOrganism: Homo sapiens (human)

-
Macromolecule #1: Solute carrier family 40 member 1

MacromoleculeName: Solute carrier family 40 member 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 66.349898 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: 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 NQANTSVVGS GLEVLFQGPG AAEDQVDPRL IDGKHHHHHH HH

-
Macromolecule #2: Fab45D8 Heavy Chain

MacromoleculeName: Fab45D8 Heavy Chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 23.852592 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: EVQLQESGPG LAKPSQTLSL TCSVTGSSIT SDYWNWIRKF PGNKLEYMGY ISYSGSTYYN PSLKSQISIT RDTSKNHYYL QLNSVTTED TATYYCARQG LRNWYFDVWG TGTTVTVSSA KTTAPSVYPL APVCGGTTGS SVTLGCLVKG YFPEPVTLTW N SGSLSSGV ...String:
EVQLQESGPG LAKPSQTLSL TCSVTGSSIT SDYWNWIRKF PGNKLEYMGY ISYSGSTYYN PSLKSQISIT RDTSKNHYYL QLNSVTTED TATYYCARQG LRNWYFDVWG TGTTVTVSSA KTTAPSVYPL APVCGGTTGS SVTLGCLVKG YFPEPVTLTW N SGSLSSGV HTFPALLQSG LYTLSSSVTV TSNTWPSQTI TCNVAHPASS TKVDKKIEPR VP

-
Macromolecule #3: Fab45D8 Light Chain

MacromoleculeName: Fab45D8 Light Chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 24.008516 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DIVLTQSPAS LPVSLGQRAT ISCRASKSVS ASAYSYMHWY QQKPGQPPKP LIYLASNLES GVPARFSGSG SGTDFTLNIH PVEEEDAAT YYCQHNRELP YTFGGGTKLE IKRADAAPTV SIFPPSSEQL TSGGASVVCF LNNFYPKDIN VKWKIDGSER Q NGVLNSWT ...String:
DIVLTQSPAS LPVSLGQRAT ISCRASKSVS ASAYSYMHWY QQKPGQPPKP LIYLASNLES GVPARFSGSG SGTDFTLNIH PVEEEDAAT YYCQHNRELP YTFGGGTKLE IKRADAAPTV SIFPPSSEQL TSGGASVVCF LNNFYPKDIN VKWKIDGSER Q NGVLNSWT DQDSKDSTYS MSSTLTLTKD EYERHNSYTC EATHKTSTSP IVKSFNRNEC

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
GridDetails: unspecified
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus max: -20.0 µm / Nominal defocus min: -8.0 µm / Nominal magnification: 105000
Specialist opticsEnergy filter - Slit width: 20 eV
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Number grids imaged: 3 / Number real images: 5415 / Average exposure time: 6.0 sec. / Average electron dose: 60.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

CTF correctionSoftware - Name: CTFFIND
Startup modelType of model: OTHER / Details: Ab initio generated 3D model from RELION
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final 3D classificationSoftware - Name: RELION
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cisTEM / Number images used: 308366

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more