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Yorodumi- PDB-7bc6: Cryo-EM structure of the outward open proton coupled folate trans... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7bc6 | |||||||||||||||||||||||||||||||||
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Title | Cryo-EM structure of the outward open proton coupled folate transporter at pH 7.5 | |||||||||||||||||||||||||||||||||
Components |
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Keywords | MEMBRANE PROTEIN / transporter folate proton symporter | |||||||||||||||||||||||||||||||||
Function / homology | Function and homology information 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 / folic acid binding / transmembrane transporter activity / transmembrane transport / basolateral plasma membrane ...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 / folic acid binding / transmembrane transporter activity / transmembrane transport / basolateral plasma membrane / endosome membrane / endosome / apical plasma membrane / plasma membrane Similarity search - Function | |||||||||||||||||||||||||||||||||
Biological species | Gallus gallus (chicken) Lama glama (llama) | |||||||||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||||||||||||||||||||||||||
Authors | Parker, J.L. / Deme, J.C. / Lea, S.M. / Newstead, S. | |||||||||||||||||||||||||||||||||
Funding support | United Kingdom, 10items
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Citation | Journal: Nature / Year: 2021 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 |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7bc6.cif.gz | 103.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7bc6.ent.gz | 77.4 KB | Display | PDB format |
PDBx/mmJSON format | 7bc6.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7bc6_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 7bc6_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 7bc6_validation.xml.gz | 33.7 KB | Display | |
Data in CIF | 7bc6_validation.cif.gz | 48.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/bc/7bc6 ftp://data.pdbj.org/pub/pdb/validation_reports/bc/7bc6 | HTTPS FTP |
-Related structure data
Related structure data | 12140MC 7bc7C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 51366.570 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Gallus gallus (chicken) / Gene: PCFT / Production host: Saccharomyces cerevisiae (brewer's yeast) / References: UniProt: E6Y8U5 |
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#2: Antibody | Mass: 13460.006 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Lama glama (llama) |
Has protein modification | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Molecular weight |
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Source (natural) |
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Source (recombinant) | Organism: Saccharomyces cerevisiae (brewer's yeast) | ||||||||||||||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 59.1 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 174399 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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