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- EMDB-64072: Cryo-EM structure of the human G6P transporter SLC37A2 in the pre... -

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Basic information

Entry
Database: EMDB / ID: EMD-64072
TitleCryo-EM structure of the human G6P transporter SLC37A2 in the presence of G6P with an asymmetric conformation.
Map data
Sample
  • Complex: SLC37A2
    • Protein or peptide: Glucose-6-phosphate exchanger SLC37A2
  • Ligand: 6-O-phosphono-alpha-D-glucopyranose
  • Ligand: water
KeywordsTransporter / G6P / MFS / ER membrane / MEMBRANE PROTEIN
Function / homology
Function and homology information


glucose 6-phosphate:phosphate antiporter activity / glucose-6-phosphate transport / Gluconeogenesis / phosphate ion transmembrane transport / endoplasmic reticulum membrane / extracellular exosome
Similarity search - Function
Glucose-6-phosphate exchanger SLC37A1/ SLC37A2 / 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 SLC37A2
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.6 Å
AuthorsSun L / Liu X / Lai Q
Funding support China, 4 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32471279 China
National Natural Science Foundation of China (NSFC)32322041 China
National Natural Science Foundation of China (NSFC)32321001 China
National Natural Science Foundation of China (NSFC)W2412029 China
CitationJournal: Nat Struct Mol Biol / Year: 2026
Title: Structural basis of glucose-6-phosphate transport by human SLC37A2.
Authors: Qinxuan Lai / Mengzhen Xu / Yongxiang Gao / Zhisen Yang / Linfeng Sun / Xin Liu /
Abstract: Glucose-6-phosphate (G6P) transporters are crucial for glucose metabolism by mediating G6P transport from the cytoplasm to endoplasmic reticulum (ER). However, their transport mechanisms remain ...Glucose-6-phosphate (G6P) transporters are crucial for glucose metabolism by mediating G6P transport from the cytoplasm to endoplasmic reticulum (ER). However, their transport mechanisms remain poorly understood. Here, we elucidate the structural and functional basis of human solute carrier family 37 member 2 (SLC37A2), a G6P transporter implicated in metabolic regulation and macrophage inflammation. We show that SLC37A2 functions as a uniporter, facilitating G6P transport independent of inorganic phosphate gradients. Structures of SLC37A2 in the apo and G6P-bound states reveal a dimeric architecture. Both the ER luminal-open and cytosolic-open structures are captured, showing the structural dynamics during G6P transport. G6P is coordinated by SLC37A2 through interactions with its phosphate and hydroxyl groups. Furthermore, mapping mutations associated with glycogen storage disease type Ib onto SLC37A2 highlights residues essential for transport activity. Together, this work provides structural insights into G6P transport and establishes a framework for understanding related metabolic disorders.
History
DepositionApr 7, 2025-
Header (metadata) releaseNov 5, 2025-
Map releaseNov 5, 2025-
UpdateMay 27, 2026-
Current statusMay 27, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_64072.png

Downloads & links

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Map

FileDownload / File: emd_64072.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.1 Å/pix.
x 256 pix.
= 281.6 Å		1.1 Å/pix.
x 256 pix.
= 281.6 Å		1.1 Å/pix.
x 256 pix.
= 281.6 Å

Surface

Projections

Slices (1/3)

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Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.1 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.3
Minimum - Maximum-1.379296 - 1.9397811
Average (Standard dev.)-0.0006236034 (±0.03867509)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 281.6 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_64072_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_64072_half_map_2.map
Projections & Slices
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Histogram

Histogram (log scale)

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Sample components

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Entire : SLC37A2

EntireName: SLC37A2
Components
  • Complex: SLC37A2
    • Protein or peptide: Glucose-6-phosphate exchanger SLC37A2
  • Ligand: 6-O-phosphono-alpha-D-glucopyranose
  • Ligand: water

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Supramolecule #1: SLC37A2

SupramoleculeName: SLC37A2 / 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 SLC37A2

MacromoleculeName: Glucose-6-phosphate exchanger SLC37A2 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 54.477105 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MRSSLAPGVW FFRAFSRDSW FRGLILLLTF LIYACYHMSR KPISIVKSRL HQNCSEQIKP INDTHSLNDT MWCSWAPFDK DNYKELLGG VDNAFLIAYA IGMFISGVFG ERLPLRYYLS AGMLLSGLFT SLFGLGYFWN IHELWYFVVI QVCNGLVQTT G WPSVVTCV ...String:
MRSSLAPGVW FFRAFSRDSW FRGLILLLTF LIYACYHMSR KPISIVKSRL HQNCSEQIKP INDTHSLNDT MWCSWAPFDK DNYKELLGG VDNAFLIAYA IGMFISGVFG ERLPLRYYLS AGMLLSGLFT SLFGLGYFWN IHELWYFVVI QVCNGLVQTT G WPSVVTCV GNWFGKGKRG FIMGIWNSHT SVGNILGSLI AGIWVNGQWG LSFIVPGIIT AVMGVITFLF LIEHPEDVDC AP PQHHGEP AENQDNPEDP GNSPCSIRES GLETVAKCSK GPCEEPAAIS FFGALRIPGV VEFSLCLLFA KLVSYTFLYW LPL YIANVA HFSAKEAGDL STLFDVGGII GGIVAGLVSD YTNGRATTCC VMLILAAPMM FLYNYIGQDG IASSIVMLII CGGL VNGPY ALITTAVSAD LGTHKSLKGN AKALSTVTAI IDGTGSIGAA LGPLLAGLIS PTGWNNVFYM LISADVLACL LLCRL VYKE ILAWKVSLSR GSGYKEI

UniProtKB: Glucose-6-phosphate exchanger SLC37A2

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

MacromoleculeName: 6-O-phosphono-alpha-D-glucopyranose / type: ligand / ID: 2 / Number of copies: 1 / Formula: G6P
Molecular weightTheoretical: 260.136 Da
Chemical component information

ChemComp-G6P:
6-O-phosphono-alpha-D-glucopyranose

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Macromolecule #3: water

MacromoleculeName: water / type: ligand / ID: 3 / Number of copies: 1 / Formula: HOH
Molecular weightTheoretical: 18.015 Da
Chemical component information

ChemComp-HOH:
WATER

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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: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOCONTINUUM (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: SPOT SCAN / Imaging mode: DIFFRACTION / 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: NONE
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. v4.2.1) / Number images used: 107465
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION
FSC plot (resolution estimation)

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