[English] 日本語
Yorodumi
- EMDB-19009: Cryo-EM structure of the inward-facing ethanolamine-bound FLVCR1 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-19009
TitleCryo-EM structure of the inward-facing ethanolamine-bound FLVCR1
Map data
Sample
  • Complex: ethanolamine-bound FLVCR1 monomer
    • Protein or peptide: Heme transporter FLVCR1
  • Ligand: ETHANOLAMINE
KeywordsMFS / ethanolamine transport / human transporter / MEMBRANE PROTEIN
Function / homology
Function and homology information


heme export / ethanolamine transmembrane transporter activity / choline transmembrane transporter activity / heme transport / heme transmembrane transporter activity / embryonic skeletal system morphogenesis / choline transport / phospholipid biosynthetic process / regulation of organ growth / head morphogenesis ...heme export / ethanolamine transmembrane transporter activity / choline transmembrane transporter activity / heme transport / heme transmembrane transporter activity / embryonic skeletal system morphogenesis / choline transport / phospholipid biosynthetic process / regulation of organ growth / head morphogenesis / Heme biosynthesis / heme biosynthetic process / embryonic digit morphogenesis / mitochondrial transport / blood vessel development / erythrocyte maturation / spleen development / erythrocyte differentiation / Iron uptake and transport / multicellular organism growth / in utero embryonic development / intracellular iron ion homeostasis / mitochondrial inner membrane / heme binding / mitochondrion / membrane / plasma membrane
Similarity search - Function
: / Major facilitator superfamily / Major Facilitator Superfamily / Major facilitator superfamily domain / Major facilitator superfamily (MFS) profile. / MFS transporter superfamily
Similarity search - Domain/homology
Choline/ethanolamine transporter FLVCR1
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.9 Å
AuthorsWeng T-H / Wu D / Safarian S
Funding support Germany, 1 items
OrganizationGrant numberCountry
Max Planck Society Germany
CitationJournal: Nature / Year: 2024
Title: Molecular mechanism of choline and ethanolamine transport in humans.
Authors: Keiken Ri / Tsai-Hsuan Weng / Ainara Claveras Cabezudo / Wiebke Jösting / Yu Zhang / Andre Bazzone / Nancy C P Leong / Sonja Welsch / Raymond T Doty / Gonca Gursu / Tiffany Jia Ying Lim / ...Authors: Keiken Ri / Tsai-Hsuan Weng / Ainara Claveras Cabezudo / Wiebke Jösting / Yu Zhang / Andre Bazzone / Nancy C P Leong / Sonja Welsch / Raymond T Doty / Gonca Gursu / Tiffany Jia Ying Lim / Sarah Luise Schmidt / Janis L Abkowitz / Gerhard Hummer / Di Wu / Long N Nguyen / Schara Safarian /
Abstract: Human feline leukaemia virus subgroup C receptor-related proteins 1 and 2 (FLVCR1 and FLVCR2) are members of the major facilitator superfamily. Their dysfunction is linked to several clinical ...Human feline leukaemia virus subgroup C receptor-related proteins 1 and 2 (FLVCR1 and FLVCR2) are members of the major facilitator superfamily. Their dysfunction is linked to several clinical disorders, including PCARP, HSAN and Fowler syndrome. Earlier studies concluded that FLVCR1 may function as a haem exporter, whereas FLVCR2 was suggested to act as a haem importer, yet conclusive biochemical and detailed molecular evidence remained elusive for the function of both transporters. Here, we show that FLVCR1 and FLVCR2 facilitate the transport of choline and ethanolamine across the plasma membrane, using a concentration-driven substrate translocation process. Through structural and computational analyses, we have identified distinct conformational states of FLVCRs and unravelled the coordination chemistry underlying their substrate interactions. Fully conserved tryptophan and tyrosine residues form the binding pocket of both transporters and confer selectivity for choline and ethanolamine through cation-π interactions. Our findings clarify the mechanisms of choline and ethanolamine transport by FLVCR1 and FLVCR2, enhance our comprehension of disease-associated mutations that interfere with these vital processes and shed light on the conformational dynamics of these major facilitator superfamily proteins during the transport cycle.
History
DepositionNov 29, 2023-
Header (metadata) releaseApr 17, 2024-
Map releaseApr 17, 2024-
UpdateJun 19, 2024-
Current statusJun 19, 2024Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_19009.png

Downloads & links

-
Map

FileDownload / File: emd_19009.map.gz / Format: CCP4 / Size: 12.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.15 Å/pix.
x 150 pix.
= 171.9 Å		1.15 Å/pix.
x 150 pix.
= 171.9 Å		1.15 Å/pix.
x 150 pix.
= 171.9 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.146 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.03
Minimum - Maximum-0.09766663 - 0.14623883
Average (Standard dev.)0.00006340703 (±0.005719892)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions150150150
Spacing150150150
CellA=B=C: 171.90001 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #1

Fileemd_19009_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_19009_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : ethanolamine-bound FLVCR1 monomer

EntireName: ethanolamine-bound FLVCR1 monomer
Components
  • Complex: ethanolamine-bound FLVCR1 monomer
    • Protein or peptide: Heme transporter FLVCR1
  • Ligand: ETHANOLAMINE

-
Supramolecule #1: ethanolamine-bound FLVCR1 monomer

SupramoleculeName: ethanolamine-bound FLVCR1 monomer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 60 KDa

-
Macromolecule #1: Heme transporter FLVCR1

MacromoleculeName: Heme transporter FLVCR1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 60.896316 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MARPDDEEGA AVAPGHPLAK GYLPLPRGAP VGKESVELQN GPKAGTFPVN GAPRDSLAAA SGVLGGPQTP LAPEEETQAR LLPAGAGAE TPGAESSPLP LTALSPRRFV VLLIFSLYSL VNAFQWIQYS IISNVFEGFY GVTLLHIDWL SMVYMLAYVP L IFPATWLL ...String:
MARPDDEEGA AVAPGHPLAK GYLPLPRGAP VGKESVELQN GPKAGTFPVN GAPRDSLAAA SGVLGGPQTP LAPEEETQAR LLPAGAGAE TPGAESSPLP LTALSPRRFV VLLIFSLYSL VNAFQWIQYS IISNVFEGFY GVTLLHIDWL SMVYMLAYVP L IFPATWLL DTRGLRLTAL LGSGLNCLGA WIKCGSVQQH LFWVTMLGQC LCSVAQVFIL GLPSRIASVW FGPKEVSTAC AT AVLGNQL GTAVGFLLPP VLVPNTQNDT NLLACNISTM FYGTSAVATL LFILTAIAFK EKPRYPPSQA QAALQDSPPE EYS YKKSIR NLFKNIPFVL LLITYGIMTG AFYSVSTLLN QMILTYYEGE EVNAGRIGLT LVVAGMVGSI LCGLWLDYTK TYKQ TTLIV YILSFIGMVI FTFTLDLRYI IIVFVTGGVL GFFMTGYLPL GFEFAVEITY PESEGTSSGL LNASAQIFGI LFTLA QGKL TSDYGPKAGN IFLCVWMFIG IILTALIKSD LRRHNINIGI TNVDVKAIPA DSPTDQEPKT VMLSKQSESA IDYKDD DDK

UniProtKB: Choline/ethanolamine transporter FLVCR1

-
Macromolecule #2: ETHANOLAMINE

MacromoleculeName: ETHANOLAMINE / type: ligand / ID: 2 / Number of copies: 1 / Formula: ETA
Molecular weightTheoretical: 61.083 Da
Chemical component information

ChemComp-ETA:
ETHANOLAMINE

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration1.5 mg/mL
BufferpH: 7.4
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 55.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.1 µm / Nominal defocus min: 1.1 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Particle selectionNumber selected: 5185344
Startup modelType of model: OTHER / Details: Ab initio reconstruction
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Algorithm: BACK PROJECTION / Resolution.type: BY AUTHOR / Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 52147
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

-
Atomic model buiding 1

Initial modelPDB ID:

8qct


Chain - Source name: PDB / Chain - Initial model type: experimental model
RefinementSpace: REAL
Output model

PDB-8r8t:
Cryo-EM structure of the inward-facing ethanolamine-bound FLVCR1

+
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