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Structure paper

TitleStructural basis of glucose-6-phosphate transport by human SLC37A2.
Journal, issue, pagesNat Struct Mol Biol, Vol. 33, Issue 1, Page 112-122, Year 2026
Publish dateNov 12, 2025
AuthorsQinxuan Lai / Mengzhen Xu / Yongxiang Gao / Zhisen Yang / Linfeng Sun / Xin Liu /
PubMed AbstractGlucose-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.
External linksNat Struct Mol Biol / PubMed:41225050
MethodsEM (single particle)
Resolution3.2 - 3.7 Å
Structure data

64048

9ucm

EMDB-64048, PDB-9ucm:
Cryo-EM structure of the human G6P transporter SLC37A2 in the apo state with a symmetric ER luminal-open conformation.
Method: EM (single particle) / Resolution: 3.2 Å

64072

9udv

EMDB-64072, PDB-9udv:
Cryo-EM structure of the human G6P transporter SLC37A2 in the presence of G6P with an asymmetric conformation.
Method: EM (single particle) / Resolution: 3.6 Å

64073

9udw

EMDB-64073, PDB-9udw:
Cryo-EM structure of the human G6P transporter SLC37A2 in the G6P bound state with a symmetric cytosolic-open conformation.
Method: EM (single particle) / Resolution: 3.5 Å

64074

9udx

EMDB-64074, PDB-9udx:
Cryo-EM structure of the human G6P transporter SLC37A2 in the presence of G6P with a symmetric ER luminal-open conformation.
Method: EM (single particle) / Resolution: 3.7 Å

Chemicals

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

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / Transporter / G6P / MFS / ER membrane

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