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Open data
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Basic information
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Title | outward-open hSLC19A1 | |||||||||
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![]() | outward-open hSLC19A1 / MEMBRANE PROTEIN | |||||||||
Function / homology | ![]() folate:monoatomic anion antiporter activity / methotrexate transport / folic acid transmembrane transporter activity / methotrexate transmembrane transporter activity / folic acid transport / folate transmembrane transport / folate import across plasma membrane / cyclic-GMP-AMP transmembrane transporter activity / cyclic-GMP-AMP transmembrane import across plasma membrane / 2',3'-cyclic GMP-AMP binding ...folate:monoatomic anion antiporter activity / methotrexate transport / folic acid transmembrane transporter activity / methotrexate transmembrane transporter activity / folic acid transport / folate transmembrane transport / folate import across plasma membrane / cyclic-GMP-AMP transmembrane transporter activity / cyclic-GMP-AMP transmembrane import across plasma membrane / 2',3'-cyclic GMP-AMP binding / organic anion transport / Metabolism of folate and pterines / xenobiotic transmembrane transport / organic anion transmembrane transporter activity / positive regulation of cGAS/STING signaling pathway / folic acid binding / antiporter activity / folic acid metabolic process / xenobiotic transmembrane transporter activity / transport across blood-brain barrier / female pregnancy / electron transport chain / brush border membrane / response to toxic substance / basolateral plasma membrane / electron transfer activity / periplasmic space / apical plasma membrane / iron ion binding / response to xenobiotic stimulus / heme binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.94 Å | |||||||||
![]() | Zhang QX / Liu KX / Gao P | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Molecular basis of SLC19A1-mediated folate and cyclic dinucleotide transport. Authors: Qixiang Zhang / Xuyuan Zhang / Kexin Liu / Yalan Zhu / Xiaohua Nie / Junxiao Ma / Panpan Sun / Zhaolong Li / Yina Gao / Songqing Liu / Ang Gao / Liguo Zhang / Pu Gao / ![]() Abstract: The solute carrier protein SLC19A1 is crucial for transporting folate nutrients, antifolate chemotherapeutics, and more recently cyclic dinucleotides (CDNs) immune transmitters, influencing various ...The solute carrier protein SLC19A1 is crucial for transporting folate nutrients, antifolate chemotherapeutics, and more recently cyclic dinucleotides (CDNs) immune transmitters, influencing various physiological and pathological processes. While the inward-open state of human SLC19A1 (hSLC19A1) has been previously described, key aspects regarding its conformational dynamics, substrate selectivity, and precise mechanisms underlying CDNs transport remain elusive. Using an antibody-facilitated conformation screening strategy, we present cryo-electron microscopy structures of hSLC19A1 in its outward-open state with and without bound substrates, revealing detailed mechanisms of substrate recognition and conformational changes during transport. We identify both general and specific features for folate/antifolate recognition, including an SLC19A1-specific pocket for accommodating γ-carboxylate-modified antifolates. Intriguingly, CDNs bind as monomers within the canonical pocket of outward-open hSLC19A1, contrasting with dimeric binding in inward-open structures. Together with functional assays, these findings provide a framework for developing antifolate drugs and CDN-targeted therapies, advancing our understanding of SLC19A1's physiological and therapeutic functions. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16.7 KB 16.7 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 7.6 KB | Display | ![]() |
Images | ![]() | 54 KB | ||
Filedesc metadata | ![]() | 5.9 KB | ||
Others | ![]() ![]() | 59.3 MB 59.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 807.9 KB | Display | ![]() |
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Full document | ![]() | 807.5 KB | Display | |
Data in XML | ![]() | 15.3 KB | Display | |
Data in CIF | ![]() | 20.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9jozMC ![]() 9jriC ![]() 9jrkC ![]() 9jrlC ![]() 9jrmC ![]() 9jrnC 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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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_61690_half_map_1.map | ||||||||||||
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Density Histograms |
-Half map: #1
File | emd_61690_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
-Entire : outward-open hSLC19A1
Entire | Name: outward-open hSLC19A1 |
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Components |
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-Supramolecule #1: outward-open hSLC19A1
Supramolecule | Name: outward-open hSLC19A1 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Soluble cytochrome b562,Reduced folate transporter,fusion protein
Macromolecule | Name: Soluble cytochrome b562,Reduced folate transporter,fusion protein type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 77.480914 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MADLEDNWET LNDNLKVIEK ADNAAQVKDA LTKMRAAALD AQKATPPKLE DKSPDSPEMK DFRHGFDILV GQIDDALKLA NEGKVKEAQ AAAEQLKTTR NAYIQKYLSW RHLVCYLCFY GFMAQIRPGE SFITPYLLGP DKQFTREQVT NEITPVLSYS Y LAVLVPVF ...String: MADLEDNWET LNDNLKVIEK ADNAAQVKDA LTKMRAAALD AQKATPPKLE DKSPDSPEMK DFRHGFDILV GQIDDALKLA NEGKVKEAQ AAAEQLKTTR NAYIQKYLSW RHLVCYLCFY GFMAQIRPGE SFITPYLLGP DKQFTREQVT NEITPVLSYS Y LAVLVPVF LLTDYLRYTP VLLLQGLSFV SVWLLLLLGH SVAHMQLMEL FYSVTMAARI AYSSYIFSLV RPARYQRVAG YS RAAVLLG VFTSSVLGQL LVTVGRVSFS TLNYISLAFL TFSVVLALFL KRPKRSLFFN RDDRGRCETS ASELERMNPG PGG KLGHAL RVACGDSVLA RMLRELGDSL RRPQLRLWSL WWVFNSAGYY LVVYYVHILW NEVDPTTNSA RVYNFAADAA STLL GAITS FAAGFVKIRW ARWSKLLIAG VTATQAGLVF LLAHTRHPSS IWLCYAAFVL FRGSYQFLVP IATFQIASSL SKELC ALVF GVNTFFATIV KTIITFIVSD VRGLGLPVRK QFQLYSVYFL ILSIIYFLGA MLDGLRHAEE EKRKAEEEKR KGSGSQ VQL QESGGGLVQP GGSLRLSCAA SGRTISRYAM SWFRQAPGKE REFVAVARRS GDGAFYADSV QGRFTVSRDD AKNTVYL QM NSLKPEDTAV YYCAIDSDTF YSGSYDYWGQ GTQVTVSSHH HHHHHHHH UniProtKB: Soluble cytochrome b562, Reduced folate transporter |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
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 TALOS ARCTICA |
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Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.0 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |