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Open data
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Basic information
Entry | Database: PDB / ID: 8hik | ||||||
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Title | The TPP-bound BRIL-SLC19A1/Fab/Nb ternary complex | ||||||
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![]() | TRANSPORT PROTEIN / SLC19A1 / RFC / transporter / folates / 5-MTHF / TPP | ||||||
Function / homology | ![]() folic acid transmembrane transporter activity / folate:monoatomic anion antiporter activity / methotrexate transport / methotrexate transmembrane transporter activity / folic acid transport / folate transmembrane transport / folate import across plasma membrane / positive regulation of cGAS/STING signaling pathway / cyclic-GMP-AMP transmembrane transporter activity / cyclic-GMP-AMP transmembrane import across plasma membrane ...folic acid transmembrane transporter activity / folate:monoatomic anion antiporter activity / methotrexate transport / methotrexate transmembrane transporter activity / folic acid transport / folate transmembrane transport / folate import across plasma membrane / positive regulation of cGAS/STING signaling pathway / cyclic-GMP-AMP transmembrane transporter activity / cyclic-GMP-AMP transmembrane import across plasma membrane / organic anion transport / 2',3'-cyclic GMP-AMP binding / organic anion transmembrane transporter activity / xenobiotic transmembrane transport / Metabolism of folate and pterines / antiporter activity / folic acid binding / xenobiotic transmembrane transporter activity / transport across blood-brain barrier / folic acid metabolic process / female pregnancy / electron transport chain / brush border membrane / basolateral plasma membrane / periplasmic space / electron transfer activity / iron ion binding / apical plasma membrane / heme binding / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.72 Å | ||||||
![]() | Zhang, Z. / Dang, Y. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Molecular mechanism of substrate recognition by folate transporter SLC19A1. Authors: Yu Dang / Dong Zhou / Xiaojuan Du / Hongtu Zhao / Chia-Hsueh Lee / Jing Yang / Yijie Wang / Changdong Qin / Zhenxi Guo / Zhe Zhang / ![]() ![]() Abstract: Folate (vitamin B) is the coenzyme involved in one-carbon transfer biochemical reactions essential for cell survival and proliferation, with its inadequacy causing developmental defects or severe ...Folate (vitamin B) is the coenzyme involved in one-carbon transfer biochemical reactions essential for cell survival and proliferation, with its inadequacy causing developmental defects or severe diseases. Notably, mammalian cells lack the ability to de novo synthesize folate but instead rely on its intake from extracellular sources via specific transporters or receptors, among which SLC19A1 is the ubiquitously expressed one in tissues. However, the mechanism of substrate recognition by SLC19A1 remains unclear. Here we report the cryo-EM structures of human SLC19A1 and its complex with 5-methyltetrahydrofolate at 3.5-3.6 Å resolution and elucidate the critical residues for substrate recognition. In particular, we reveal that two variant residues among SLC19 subfamily members designate the specificity for folate. Moreover, we identify intracellular thiamine pyrophosphate as the favorite coupled substrate for folate transport by SLC19A1. Together, this work establishes the molecular basis of substrate recognition by this central folate transporter. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 195.7 KB | Display | ![]() |
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PDB format | ![]() | 152.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 34819MC ![]() 8hiiC ![]() 8hijC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
#1: Protein | Mass: 75110.344 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Gene: cybC, SLC19A1, FLOT1, RFC1 / Production host: ![]() |
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#2: Antibody | Mass: 27759.207 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#3: Antibody | Mass: 16673.551 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
#4: Antibody | Mass: 25575.604 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#5: Chemical | ChemComp-TPP / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: The TPP-bound BRIL-SLC19A1/Fab/Nb ternary complex / Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1500 nm / Nominal defocus min: 700 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.72 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 229158 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||
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