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- EMDB-12140: Cryo-EM structure of the outward open proton coupled folate trans... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-12140 | |||||||||||||||||||||||||||||||||
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Title | Cryo-EM structure of the outward open proton coupled folate transporter at pH 7.5 | |||||||||||||||||||||||||||||||||
![]() | globally sharpened map from cryosparc non uniform refinement | |||||||||||||||||||||||||||||||||
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Function / homology | ![]() folic acid:proton symporter activity / Metabolism of folate and pterines / Heme signaling / Iron uptake and transport / methotrexate transmembrane transporter activity / folate import across plasma membrane / ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||||||||||||||||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() | |||||||||||||||||||||||||||||||||
Method | ![]() ![]() | |||||||||||||||||||||||||||||||||
![]() | Parker JL / Deme JC / Lea SM / Newstead S | |||||||||||||||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis of antifolate recognition and transport by PCFT. Authors: Joanne L Parker / Justin C Deme / Gabriel Kuteyi / Zhiyi Wu / Jiandong Huo / I David Goldman / Raymond J Owens / Philip C Biggin / Susan M Lea / Simon Newstead / ![]() ![]() Abstract: Folates (also known as vitamin B9) have a critical role in cellular metabolism as the starting point in the synthesis of nucleic acids, amino acids and the universal methylating agent S- ...Folates (also known as vitamin B9) have a critical role in cellular metabolism as the starting point in the synthesis of nucleic acids, amino acids and the universal methylating agent S-adenylsmethionine. Folate deficiency is associated with a number of developmental, immune and neurological disorders. Mammals cannot synthesize folates de novo; several systems have therefore evolved to take up folates from the diet and distribute them within the body. The proton-coupled folate transporter (PCFT) (also known as SLC46A1) mediates folate uptake across the intestinal brush border membrane and the choroid plexus, and is an important route for the delivery of antifolate drugs in cancer chemotherapy. How PCFT recognizes folates or antifolate agents is currently unclear. Here we present cryo-electron microscopy structures of PCFT in a substrate-free state and in complex with a new-generation antifolate drug (pemetrexed). Our results provide a structural basis for understanding antifolate recognition and provide insights into the pH-regulated mechanism of folate transport mediated by PCFT. | |||||||||||||||||||||||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 64.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 20.2 KB 20.2 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 11.4 KB | Display | ![]() |
Images | ![]() | 119.3 KB | ||
Masks | ![]() | 125 MB | ![]() | |
Others | ![]() ![]() ![]() | 62.6 MB 115.8 MB 115.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7bc6MC ![]() 7bc7C M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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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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Annotation | globally sharpened map from cryosparc non uniform refinement | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.832 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
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Projections & Slices |
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Density Histograms |
-Additional map: unsharpened map from cryosparc non uniform refinement
File | emd_12140_additional_1.map | ||||||||||||
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Annotation | unsharpened map from cryosparc non uniform refinement | ||||||||||||
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Density Histograms |
-Half map: half map B from cryosparc non uniform refinement
File | emd_12140_half_map_1.map | ||||||||||||
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Annotation | half map B from cryosparc non uniform refinement | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map A from cryosparc non uniform refinement
File | emd_12140_half_map_2.map | ||||||||||||
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Annotation | half map A from cryosparc non uniform refinement | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Complex of the outward open proton coupled folate transporter wit...
Entire | Name: Complex of the outward open proton coupled folate transporter with nanobody at pH 7.5 |
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Components |
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-Supramolecule #1: Complex of the outward open proton coupled folate transporter wit...
Supramolecule | Name: Complex of the outward open proton coupled folate transporter with nanobody at pH 7.5 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: proton-coupled folate transporter
Supramolecule | Name: proton-coupled folate transporter / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() ![]() |
-Supramolecule #3: nanobody
Supramolecule | Name: nanobody / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: ![]() ![]() ![]() |
-Macromolecule #1: Proton-coupled folate transporter
Macromolecule | Name: Proton-coupled folate transporter / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() ![]() |
Molecular weight | Theoretical: 51.36657 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MAAPSDPPTA ATPPAPPPPA RRCLPAPSVE PLLFLATLAL GLQVPLATQY LWDRLGAERG YVGPNASSPH GCGNGSGAVD PLREEVEAL VAHWNLCINL GGFFVGLFSV TLFGPWSDSV GRRPVLVLPA VGMAVQAAVY LLVMYLRLHV AYLLLGRIIS G LLGDYNLI ...String: MAAPSDPPTA ATPPAPPPPA RRCLPAPSVE PLLFLATLAL GLQVPLATQY LWDRLGAERG YVGPNASSPH GCGNGSGAVD PLREEVEAL VAHWNLCINL GGFFVGLFSV TLFGPWSDSV GRRPVLVLPA VGMAVQAAVY LLVMYLRLHV AYLLLGRIIS G LLGDYNLI LAGCFASVAD SSNQRTRTFR VAILEACLGV AGMVASVGGG QWRKAEGYIN PFWLVLAASL AAALYAALCL QE TVKQRRA AKLLTLQHYK AVYKLYTAPE DLSSRRKLAL YSLAFFLLVT VHFGTKDLYV LYELGSPLCW ASDLIGYGSA ASY LAYLSS LGGLRLLQLC LEDTWVAEIG LISNIAGLVV ISLATTTPLM FTGYGIMFLS MAATPVIRAK LSKLVSETEQ GALF ASVAC VEGLCSLVAT GVFNSLYPST LHFMRGFPFL FGAILLLIPA AIMGWIEIQD SNLQYSHFSD ASSSPADGGE NLYFQ |
-Macromolecule #2: nanobody
Macromolecule | Name: nanobody / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() ![]() |
Molecular weight | Theoretical: 13.460006 KDa |
Sequence | String: GPSQVQLVES GGGLVQPGGS LRLSCAASGF TFSRYWMYWV RQAPGKGPEW LSHMNPSGSD IKYTDSVKGR FTISRDNAKN TLYLQMNSL KPDDTAVYYC VADRRALGSP EYWGQGTQVT VSSA |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 59.1 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |