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Structural basis of phosphate export by human XPR1

Author

Listed:
  • Qixian He

    (Yunnan University)

  • Ran Zhang

    (Fudan University)

  • Sandrine Tury

    (Université Montpellier)

  • Valérie Courgnaud

    (Université Montpellier)

  • Fenglian Liu

    (Yunnan University)

  • Jean-luc Battini

    (Université Montpellier)

  • Baobin Li

    (Fudan University)

  • Qingfeng Chen

    (Yunnan University)

Abstract

Phosphorus in crucial for all living organisms. In vertebrate, cellular phosphate homeostasis is partly controlled by XPR1, a poorly characterized inositol pyrophosphate-dependent phosphate exporter. Here, we report the cryo-EM structure of human XPR1, which forms a loose dimer with 10 transmembrane helices (TM) in each protomer. The structure consists of a scaffold domain (TM1, TM3-4) and a core domain (TM2, TM5-10) structurally related to ion-translocating rhodopsins. Bound phosphate is observed in a tunnel within the core domain at a narrow point that separates the tunnel into intracellular and extracellular vestibules. This site contains a cluster of basic residues that coordinate phosphate and a conserved W573 essential for export function. Loss of inositol pyrophosphate binding is accompanied by structural movements in TM9 and the W573 sidechain, closing the extracellular vestibule and blocking phosphate export. These findings provide insight into XPR1 mechanism and pave the way for further in-depth XPR1 studies.

Suggested Citation

  • Qixian He & Ran Zhang & Sandrine Tury & Valérie Courgnaud & Fenglian Liu & Jean-luc Battini & Baobin Li & Qingfeng Chen, 2025. "Structural basis of phosphate export by human XPR1," Nature Communications, Nature, vol. 16(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-55995-8
    DOI: 10.1038/s41467-025-55995-8
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    References listed on IDEAS

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    1. Bjørn P. Pedersen & Hemant Kumar & Andrew B. Waight & Aaron J. Risenmay & Zygy Roe-Zurz & Bryant H. Chau & Avner Schlessinger & Massimiliano Bonomi & William Harries & Andrej Sali & Atul K. Johri & Ro, 2013. "Crystal structure of a eukaryotic phosphate transporter," Nature, Nature, vol. 496(7446), pages 533-536, April.
    2. Rui Yan & Huiwen Chen & Chuanyu Liu & Jun Zhao & Di Wu & Juquan Jiang & Jianke Gong & Daohua Jiang, 2024. "Human XPR1 structures reveal phosphate export mechanism," Nature, Nature, vol. 633(8031), pages 960-967, September.
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    Cited by:

    1. Long Chen & Jin He & Mingxing Wang & Ji She, 2025. "Structure and function of human XPR1 in phosphate export," Nature Communications, Nature, vol. 16(1), pages 1-8, December.

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