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Open data
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Basic information
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Title | Cryo-EM structure of the inward-facing FLVCR2 | |||||||||
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![]() | MFS / choline transport / human transporter / MEMBRANE PROTEIN | |||||||||
Function / homology | ![]() heme export / heme transmembrane transporter activity / mitochondrial membrane / endoplasmic reticulum membrane / heme binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
![]() | Weng T-H / Wu D / Safarian S | |||||||||
Funding support | ![]()
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![]() | ![]() 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 |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 7.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16.3 KB 16.3 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 5.8 KB | Display | ![]() |
Images | ![]() | 104.9 KB | ||
Filedesc metadata | ![]() | 6 KB | ||
Others | ![]() ![]() | 13.5 MB 13.5 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8qcxMC ![]() 8qcsC ![]() 8qctC ![]() 8qcyC ![]() 8qd0C ![]() 8r8tC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.146 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_18336_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_18336_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : FLVCR2 monomer
Entire | Name: FLVCR2 monomer |
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Components |
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-Supramolecule #1: FLVCR2 monomer
Supramolecule | Name: FLVCR2 monomer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 58 KDa |
-Macromolecule #1: Heme transporter FLVCR2
Macromolecule | Name: Heme transporter FLVCR2 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 58.277094 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MVNEGPNQEE SDDTPVPESA LQADPSVSVH PSVSVHPSVS INPSVSVHPS SSAHPSALAQ PSGLAHPSSS GPEDLSVIKV SRRRWAVVL VFSCYSMCNS FQWIQYGSIN NIFMHFYGVS AFAIDWLSMC YMLTYIPLLL PVAWLLEKFG LRTIALTGSA L NCLGAWVK ...String: MVNEGPNQEE SDDTPVPESA LQADPSVSVH PSVSVHPSVS INPSVSVHPS SSAHPSALAQ PSGLAHPSSS GPEDLSVIKV SRRRWAVVL VFSCYSMCNS FQWIQYGSIN NIFMHFYGVS AFAIDWLSMC YMLTYIPLLL PVAWLLEKFG LRTIALTGSA L NCLGAWVK LGSLKPHLFP VTVVGQLICS VAQVFILGMP SRIASVWFGA NEVSTACSVA VFGNQLGIAI GFLVPPVLVP NI EDRDELA YHISIMFYII GGVATLLLIL VIIVFKEKPK YPPSRAQSLS YALTSPDASY LGSIARLFKN LNFVLLVITY GLN AGAFYA LSTLLNRMVI WHYPGEEVNA GRIGLTIVIA GMLGAVISGI WLDRSKTYKE TTLVVYIMTL VGMVVYTFTL NLGH LWVVF ITAGTMGFFM TGYLPLGFEF AVELTYPESE GISSGLLNIS AQVFGIIFTI SQGQIIDNYG TKPGNIFLCV FLTLG AALT AFIKADLRRQ KANKETLENK LQEEEEESNT SKVPTAVSED HLDYKDDDDK UniProtKB: Heme transporter FLVCR2 |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 1.5 mg/mL |
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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 |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 80.0 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 |