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Structure and transport mechanism of the human prostaglandin transporter SLCO2A1

Author

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  • Zhanyi Xia

    (Ningxia Medical University
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Guangyuan Lu

    (Ningxia Medical University
    Chinese Academy of Sciences)

  • Di Wu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Jun Zhao

    (Peking University Institute of Advanced Agricultural Sciences)

  • Bowen Zhang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Haoran Xu

    (Chinese Academy of Sciences
    the First Affiliated Hospital of Anhui Medical University)

  • Yingying Du

    (the First Affiliated Hospital of Anhui Medical University)

  • Daohua Jiang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

Abstract

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 PGE2-bound forms, revealing the detailed structural features and structural basis for PGs transport. Fatty acid-like PGE2 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 PGE2 recognition, substrate selectivity, conformational changes, and pathology of SLCO2A1.

Suggested Citation

  • Zhanyi Xia & Guangyuan Lu & Di Wu & Jun Zhao & Bowen Zhang & Haoran Xu & Yingying Du & Daohua Jiang, 2025. "Structure and transport mechanism of the human prostaglandin transporter SLCO2A1," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63615-8
    DOI: 10.1038/s41467-025-63615-8
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