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Open data
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Basic information
| Entry | ![]() | |||||||||
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| Title | Human SLC37A4 lateral dimer | |||||||||
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Sample |
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Keywords | SLC37A4 / G6PT / G6P / GSD-Ib / TRANSPORT PROTEIN | |||||||||
| Function / homology | Function and homology informationglucose-6-phosphate transmembrane transporter activity / Glycogen storage disease type Ib (SLC37A4) / glucose 6-phosphate:phosphate antiporter activity / glucose-6-phosphate transport / Gluconeogenesis / phosphate ion transmembrane transport / gluconeogenesis / electron transport chain / glucose metabolic process / glucose homeostasis ...glucose-6-phosphate transmembrane transporter activity / Glycogen storage disease type Ib (SLC37A4) / glucose 6-phosphate:phosphate antiporter activity / glucose-6-phosphate transport / Gluconeogenesis / phosphate ion transmembrane transport / gluconeogenesis / electron transport chain / glucose metabolic process / glucose homeostasis / periplasmic space / electron transfer activity / iron ion binding / heme binding / endoplasmic reticulum membrane / endoplasmic reticulum / membrane Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) / ![]() | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
Authors | Zhou D / Zhang Z | |||||||||
| Funding support | China, 2 items
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Citation | Journal: Nat Struct Mol Biol / Year: 2025Title: Structural basis of G6P/Pi transport and inhibition in SLC37A4. Authors: Dong Zhou / Yang Zhang / Nanhao Chen / Shitang Huang / Chen Song / Zhe Zhang / ![]() Abstract: Glycogen storage disease type Ib (GSD-Ib), caused by loss-of-function mutations in the endoplasmic reticulum transporter SLC37A4, disrupts glucose homeostasis through impaired glucose-6-phosphate ...Glycogen storage disease type Ib (GSD-Ib), caused by loss-of-function mutations in the endoplasmic reticulum transporter SLC37A4, disrupts glucose homeostasis through impaired glucose-6-phosphate (G6P)/phosphate (Pi) antiport. Despite its central role in glycogen metabolism and immune regulation, the structural mechanisms governing SLC37A4's transport cycle and pathological dysfunction remain elusive. Here we report cryo-electron microscopy structures of human SLC37A4 in four functional states, capturing conformational transitions between lumen-facing and cytoplasm-facing states. Combined with mutational analysis, molecular dynamics simulations and functional assays, we identify a conserved substrate-binding pocket that alternately accommodates G6P and Pi through electrostatic complementarity and domain-dependent interactions. We further demonstrate that the high-affinity inhibitor S-4048 sterically occludes the cytoplasmic entry pathway by trapping the transporter in a cytoplasm-facing conformation. Our work elucidates the molecular pathology of GSD-Ib-linked mutations and provides a structural framework for developing therapies targeting this transporter in metabolic diseases. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_65554.map.gz | 168 MB | EMDB map data format | |
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| Header (meta data) | emd-65554-v30.xml emd-65554.xml | 15.1 KB 15.1 KB | Display Display | EMDB header |
| Images | emd_65554.png | 92.7 KB | ||
| Filedesc metadata | emd-65554.cif.gz | 5.7 KB | ||
| Others | emd_65554_half_map_1.map.gz emd_65554_half_map_2.map.gz | 164.7 MB 164.7 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-65554 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-65554 | HTTPS FTP |
-Validation report
| Summary document | emd_65554_validation.pdf.gz | 1.1 MB | Display | EMDB validaton report |
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| Full document | emd_65554_full_validation.pdf.gz | 1.1 MB | Display | |
| Data in XML | emd_65554_validation.xml.gz | 14.8 KB | Display | |
| Data in CIF | emd_65554_validation.cif.gz | 17.4 KB | Display | |
| Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-65554 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-65554 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9w1qMC ![]() 9w1nC ![]() 9w1oC ![]() 9w1pC ![]() 9w1rC M: atomic model generated by this map C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_65554.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Half map: #1
| File | emd_65554_half_map_1.map | ||||||||||||
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| Density Histograms |
-Half map: #2
| File | emd_65554_half_map_2.map | ||||||||||||
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| Density Histograms |
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Sample components
-Entire : Human SLC37A4
| Entire | Name: Human SLC37A4 |
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| Components |
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-Supramolecule #1: Human SLC37A4
| Supramolecule | Name: Human SLC37A4 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 120 KDa |
-Macromolecule #1: Glucose-6-phosphate exchanger SLC37A4,Soluble cytochrome b562
| Macromolecule | Name: Glucose-6-phosphate exchanger SLC37A4,Soluble cytochrome b562 type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 60.194102 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: MAAQGYGYYR TVIFSAMFGG YSLYYFNRKT FSFVMPSLVE EIPLDKDDLG FITSSQSAAY AISKFVSGVL SDQMSARWLF SSGLLLVGL VNIFFAWSST VPVFAALWFL NGLAQGLGWP PCGKVLRKWF EPSQFGTWWA ILSTSMNLAG GLGPILATIL A QSYSWRST ...String: MAAQGYGYYR TVIFSAMFGG YSLYYFNRKT FSFVMPSLVE EIPLDKDDLG FITSSQSAAY AISKFVSGVL SDQMSARWLF SSGLLLVGL VNIFFAWSST VPVFAALWFL NGLAQGLGWP PCGKVLRKWF EPSQFGTWWA ILSTSMNLAG GLGPILATIL A QSYSWRST LALSGALCVV VSFLCLLLIH NEPADVGLRN LDPMPSEGKK GSLKEESTLQ ELLLSPYLWV LSTGYLVVFG VK TCCTDWG QFFLIQEKGQ SALVGSSYMS ALEVGGLVGS IAAGYLSDRA MAKAGLSNYG NPRHGLLLFM MAGMTVSMYL FRV TVTSDS PKLWILVLGA VFGFSSYGPI ALFGVIANES APPNLCGTSH AIVGLMANVG GFLAGLPFST IAKHYSWSTA FWVA EVICA ASTAAFFLLR AEEEKRKAEE EKRKAEEEKR KADLEDNWET LNDNLKVIEK ADNAAQVKDA LTKMRAAALD AQKAT PPKL EDKSPDSPEM KDFRHGFDIL VGQIDDALKL ANEGKVKEAQ AAAEQLKTTR NAYIQKYLSN SLEVLFQ UniProtKB: Glucose-6-phosphate exchanger SLC37A4, Soluble cytochrome b562 |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Concentration | 6 mg/mL |
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| Buffer | pH: 7.5 |
| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | FEI POLARA 300 |
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| Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |
| Experimental equipment | ![]() Model: Tecnai Polara / Image courtesy: FEI Company |
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About Yorodumi




Keywords
Homo sapiens (human)
Authors
China, 2 items
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Processing
FIELD EMISSION GUN
