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TitleStructure and transport mechanism of the human prostaglandin transporter SLCO2A1.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 8124, Year 2025
Publish dateAug 30, 2025
AuthorsZhanyi Xia / Guangyuan Lu / Di Wu / Jun Zhao / Bowen Zhang / Haoran Xu / Yingying Du / Daohua Jiang /
PubMed AbstractSLCO2A1 is a member of the organic anion transporting polypeptide (OATP) family, which preferentially transports prostaglandins (PGs) into cells and plays a vital role in regulating PGs inactivation ...SLCO2A1 is a member of the organic anion transporting polypeptide (OATP) family, which preferentially transports prostaglandins (PGs) into cells and plays a vital role in regulating PGs inactivation and distribution. Dysregulation or genetic mutation of SLCO2A1 is associated with primary hypertrophic osteoarthropathy (PHO) and chronic enteropathy associated with the SLCO2A1 gene (CEAS). Although the biophysical and biochemical properties of SLCO2A1 have been characterized, the precise mechanism by which SLCO2A1 recognizes and transports PGs remains unclear. Here, we present the cryo-electron microscopy structures of human SLCO2A1 in apo and PGE-bound forms, revealing the detailed structural features and structural basis for PGs transport. Fatty acid-like PGE binds in the central cavity, engaging in specific interactions with W565 and two serine residues, which are not conserved in other OATPs. Combined with functional assays and structural comparisons, this study offers mechanistic insights into PGE recognition, substrate selectivity, conformational changes, and pathology of SLCO2A1.
External linksNat Commun / PubMed:40885756 / PubMed Central
MethodsEM (single particle)
Resolution3.1 - 3.2 Å
Structure data

61834

9juq

EMDB-61834, PDB-9juq:
Cryo-EM structure of transporter2a1
Method: EM (single particle) / Resolution: 3.2 Å

61836

9jv1

EMDB-61836, PDB-9jv1:
Cryo-EM structure of transporter2a1_PGE2
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

ChemComp-P2E:
(Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxo-cyclopentyl]hept-5-enoic acid / medication*YM

Source
  • homo sapiens (human)
KeywordsTRANSPORT PROTEIN / MFS family transporter / MFS transporter

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