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Open data
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Basic information
| Entry | Database: PDB / ID: 9w1p | |||||||||
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| Title | G6P-bound human SLC37A4 lateral dimer | |||||||||
Components | Glucose-6-phosphate exchanger SLC37A4,Soluble cytochrome b562 | |||||||||
Keywords | TRANSPORT PROTEIN / SLC37A4 / G6PT / G6P / GSD-Ib | |||||||||
| 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 / electron transfer activity / periplasmic space / iron ion binding / heme binding / endoplasmic reticulum membrane / endoplasmic reticulum / membrane Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human)![]() | |||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
Authors | Zhou, D. / Zhang, Z. | |||||||||
| Funding support | China, 2items
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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
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 9w1p.cif.gz | 146.5 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb9w1p.ent.gz | 113.9 KB | Display | PDB format |
| PDBx/mmJSON format | 9w1p.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 9w1p_validation.pdf.gz | 1.7 MB | Display | wwPDB validaton report |
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| Full document | 9w1p_full_validation.pdf.gz | 1.7 MB | Display | |
| Data in XML | 9w1p_validation.xml.gz | 35.1 KB | Display | |
| Data in CIF | 9w1p_validation.cif.gz | 50.3 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/w1/9w1p ftp://data.pdbj.org/pub/pdb/validation_reports/w1/9w1p | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 65553MC ![]() 9w1nC ![]() 9w1oC ![]() 9w1qC ![]() 9w1rC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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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: 60194.102 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human), (gene. exp.) ![]() Gene: SLC37A4, G6PT, G6PT1, PRO0685, TRG19, cybC / Production host: Homo sapiens (human) / References: UniProt: O43826, UniProt: P0ABE7#2: Sugar | Has ligand of interest | Y | Has protein modification | N | |
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-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: G6P-bound SLC37A4 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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| Molecular weight | Value: 0.12 MDa / Experimental value: NO |
| Source (natural) | Organism: Homo sapiens (human) |
| Source (recombinant) | Organism: Homo sapiens (human) |
| Buffer solution | pH: 7.5 |
| Specimen | Conc.: 6 mg/ml / 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: Tecnai Polara / Image courtesy: FEI Company |
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| Microscopy | Model: FEI POLARA 300 |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm |
| Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
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| CTF correction | Type: NONE | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 65132 / Symmetry type: POINT | ||||||||||||||||||||||||
| Refine LS restraints |
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About Yorodumi




Homo sapiens (human)

China, 2items
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FIELD EMISSION GUN