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- EMDB-62602: Cryo-EM structure of human G6PT in complex with G6P -

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Basic information

Entry
Database: EMDB / ID: EMD-62602
TitleCryo-EM structure of human G6PT in complex with G6P
Map data
Sample
  • Complex: G6PT-G6P
    • Protein or peptide: Glucose-6-phosphate exchanger SLC37A4
  • Ligand: 6-O-phosphono-beta-D-glucopyranose
KeywordsG6PT / cryo-EM / G6P / TRANSPORT PROTEIN
Function / homology
Function and homology information


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 / glucose metabolic process / glucose homeostasis / endoplasmic reticulum membrane ...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 / glucose metabolic process / glucose homeostasis / endoplasmic reticulum membrane / endoplasmic reticulum / membrane
Similarity search - Function
Glycerate/sugar phosphate transporter, conserved site / : / glpT family of transporters signature. / Sugar phosphate transporter / Major facilitator superfamily / Major Facilitator Superfamily / Major facilitator superfamily domain / Major facilitator superfamily (MFS) profile. / MFS transporter superfamily
Similarity search - Domain/homology
Glucose-6-phosphate exchanger SLC37A4
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.6 Å
AuthorsJiang DH / Xia ZY
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)31971134 China
CitationJournal: Nat Commun / Year: 2025
Title: Structural basis for transport and inhibition of the human glucose-6-phosphate transporter G6PT.
Authors: Zhanyi Xia / Yaqi Wang / Di Wu / Cheng Chi / Chen Li / Ligong Chen / Daohua Jiang /
Abstract: The human glucose-6-phosphate transporter (G6PT) moves glucose-6-phosphate (G6P) into the lumen of endoplasmic reticulum, playing a vital role in glucose homeostasis. Dysregulation of G6PT causes ...The human glucose-6-phosphate transporter (G6PT) moves glucose-6-phosphate (G6P) into the lumen of endoplasmic reticulum, playing a vital role in glucose homeostasis. Dysregulation of G6PT causes glycogen storage disease 1b. Despite its functional importance, the structure, G6P recognition, and inhibition mechanism of G6PT remain unclear. Here, we report the cryo-EM structures of human G6PT in apo, G6P-bound, and the specific inhibitor chlorogenic acid (CHA)-bound forms, elucidating the structural basis for G6PT transport and inhibition. The G6P pocket comprises subsite A for phosphate and subsite B for glucose. The CHA occupies the G6P site and locks G6PT in a partly-occluded state. Functional assays demonstrate that G6PT activity is enhanced by co-expression of glucose-6-phosphatase (G6PC), but G6PT does not form a complex with G6PC. Together, this study provides a solid foundation for understanding the structure‒function relationships and pathology of G6PT and sheds light on the future development of potential therapeutics targeting G6PT.
History
DepositionDec 5, 2024-
Header (metadata) releaseNov 12, 2025-
Map releaseNov 12, 2025-
UpdateNov 12, 2025-
Current statusNov 12, 2025Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_62602.png

Downloads & links

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Map

FileDownload / File: emd_62602.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
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Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.85 Å/pix.
x 320 pix.
= 272. Å		0.85 Å/pix.
x 320 pix.
= 272. Å		0.85 Å/pix.
x 320 pix.
= 272. Å

Surface

Projections

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Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.85 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.168
Minimum - Maximum-1.3301815 - 1.6819102
Average (Standard dev.)0.0002971888 (±0.02381274)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 272.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_62602_half_map_1.map
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_62602_half_map_2.map
Projections & Slices
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Sample components

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Entire : G6PT-G6P

EntireName: G6PT-G6P
Components
  • Complex: G6PT-G6P
    • Protein or peptide: Glucose-6-phosphate exchanger SLC37A4
  • Ligand: 6-O-phosphono-beta-D-glucopyranose

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Supramolecule #1: G6PT-G6P

SupramoleculeName: G6PT-G6P / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Glucose-6-phosphate exchanger SLC37A4

MacromoleculeName: Glucose-6-phosphate exchanger SLC37A4 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 46.391809 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: 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 NIRTKMGRVS KKAE

UniProtKB: Glucose-6-phosphate exchanger SLC37A4

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Macromolecule #2: 6-O-phosphono-beta-D-glucopyranose

MacromoleculeName: 6-O-phosphono-beta-D-glucopyranose / type: ligand / ID: 2 / Number of copies: 1 / Formula: BG6
Molecular weightTheoretical: 260.136 Da
Chemical component information

ChemComp-BG6:
6-O-phosphono-beta-D-glucopyranose

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 151770
Initial angle assignmentType: RANDOM ASSIGNMENT
Final angle assignmentType: MAXIMUM LIKELIHOOD

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