Structural basis of phosphate export by human XPR1
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 tran...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-55995-8 |
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| author | Qixian He Ran Zhang Sandrine Tury Valérie Courgnaud Fenglian Liu Jean-luc Battini Baobin Li Qingfeng Chen |
| author_facet | Qixian He Ran Zhang Sandrine Tury Valérie Courgnaud Fenglian Liu Jean-luc Battini Baobin Li Qingfeng Chen |
| author_sort | Qixian He |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3f964223997b462f885d29dde2dd89c3 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-3f964223997b462f885d29dde2dd89c32025-01-19T12:30:30ZengNature PortfolioNature Communications2041-17232025-01-0116111010.1038/s41467-025-55995-8Structural basis of phosphate export by human XPR1Qixian He0Ran Zhang1Sandrine Tury2Valérie Courgnaud3Fenglian Liu4Jean-luc Battini5Baobin Li6Qingfeng Chen7Center for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan UniversityDepartment of Anesthesiology, Zhongshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan UniversityInstitut de Recherche en Infectiologie de Montpellier IRIM - CNRS UMR 9004, Université MontpellierInstitut de Génétique Moléculaire de Montpellier IGMM - CNRS UMR 5535, Université MontpellierCenter for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan UniversityInstitut de Recherche en Infectiologie de Montpellier IRIM - CNRS UMR 9004, Université MontpellierDepartment of Anesthesiology, Zhongshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan UniversityCenter for Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan UniversityAbstract 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.https://doi.org/10.1038/s41467-025-55995-8 |
| spellingShingle | Qixian He Ran Zhang Sandrine Tury Valérie Courgnaud Fenglian Liu Jean-luc Battini Baobin Li Qingfeng Chen Structural basis of phosphate export by human XPR1 Nature Communications |
| title | Structural basis of phosphate export by human XPR1 |
| title_full | Structural basis of phosphate export by human XPR1 |
| title_fullStr | Structural basis of phosphate export by human XPR1 |
| title_full_unstemmed | Structural basis of phosphate export by human XPR1 |
| title_short | Structural basis of phosphate export by human XPR1 |
| title_sort | structural basis of phosphate export by human xpr1 |
| url | https://doi.org/10.1038/s41467-025-55995-8 |
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