+
Open data
-
Basic information
Entry | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of the inward-facing choline-bound FLVCR1 | |||||||||
![]() | ||||||||||
![]() |
| |||||||||
![]() | MFS / choline transport / human transporter / MEMBRANE PROTEIN | |||||||||
Function / homology | ![]() heme export / heme transport / heme transmembrane transporter activity / embryonic skeletal system morphogenesis / head morphogenesis / regulation of organ growth / Heme biosynthesis / heme biosynthetic process / embryonic digit morphogenesis / mitochondrial transport ...heme export / heme transport / heme transmembrane transporter activity / embryonic skeletal system morphogenesis / head morphogenesis / regulation of organ growth / 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 / intracellular iron ion homeostasis / in utero embryonic development / mitochondrial inner membrane / heme binding / mitochondrion / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.6 Å | |||||||||
![]() | Weng T-H / Wu D / Safarian S | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() 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 |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 1 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 16.2 KB 16.2 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 5.2 KB | Display | ![]() |
Images | ![]() | 119.5 KB | ||
Filedesc metadata | ![]() | 6.2 KB | ||
Others | ![]() ![]() | 8.6 MB 8.6 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8qctMC ![]() 8qcsC ![]() 8qcxC ![]() 8qcyC ![]() 8qd0C ![]() 8r8tC M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 1.146 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: #2
File | emd_18335_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #1
File | emd_18335_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : choline-bound FLVCR1 monomer
Entire | Name: choline-bound FLVCR1 monomer |
---|---|
Components |
|
-Supramolecule #1: choline-bound FLVCR1 monomer
Supramolecule | Name: choline-bound FLVCR1 monomer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 60 KDa |
-Macromolecule #1: Heme transporter FLVCR1
Macromolecule | Name: Heme transporter FLVCR1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 60.896316 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: 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: Heme transporter FLVCR1 |
-Macromolecule #2: CHOLINE ION
Macromolecule | Name: CHOLINE ION / type: ligand / ID: 2 / Number of copies: 1 / Formula: CHT |
---|---|
Molecular weight | Theoretical: 104.171 Da |
Chemical component information | ![]() ChemComp-CHT: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Concentration | 1.5 mg/mL |
---|---|
Buffer | pH: 7.4 |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 90 sec. |
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 55.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination 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 |