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-Structure paper
| タイトル | Transport and InsP gating mechanisms of the human inorganic phosphate exporter XPR1. |
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| ジャーナル・号・ページ | Nat Commun, Vol. 16, Issue 1, Page 2770, Year 2025 |
| 掲載日 | 2025年3月20日 |
著者 | Qinyu Zhu / Madeleine F Yaggi / Nikolaus Jork / Henning J Jessen / Melinda M Diver / ![]() |
| PubMed 要旨 | Inorganic phosphate (Pi) has essential metabolic and structural roles in living organisms. The Pi exporter, XPR1/SLC53A1, is critical for cellular Pi homeostasis. When intercellular Pi is high, cells ...Inorganic phosphate (Pi) has essential metabolic and structural roles in living organisms. The Pi exporter, XPR1/SLC53A1, is critical for cellular Pi homeostasis. When intercellular Pi is high, cells accumulate inositol pyrophosphate (1,5-InsP), a signaling molecule required for XPR1 function. Inactivating XPR1 mutations lead to brain calcifications, causing neurological symptoms including movement disorders, psychosis, and dementia. Here, cryo-electron microscopy structures of dimeric XPR1 and functional characterization delineate the substrate translocation pathway and how InsP initiates Pi transport. Binding of InsP to XPR1, but not the related inositol polyphosphate InsP, rigidifies the intracellular SPX domains, with InsP bridging the dimers and SPX and transmembrane domains. Locked in this state, the C-terminal tail is sequestered, revealing the entrance to the transport pathway, thus explaining the obligate roles of the SPX domain and InsP. Together, these findings advance our understanding of XPR1 transport activity and expand opportunities for rationalizing disease mechanisms and therapeutic intervention. |
リンク | Nat Commun / PubMed:40113814 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.52 - 3.3 Å |
| 構造データ | ![]() EMDB-47207: Structure of the phosphate exporter XPR1/SLC53A1, high Pi and InsP6-bound EMDB-47208: Structure of the phosphate exporter XPR1/SLC53A1, apo state EMDB-47209: Structure of the phosphate exporter XPR1/SLC53A1, apo state, rotated dimer EMDB-47210, PDB-9dvl: EMDB-47211: Structure of the phosphate exporter XPR1/SLC53A1, InsP8-bound, inward-open/occluded state EMDB-47212: Structure of the phosphate exporter XPR1/SLC53A1, InsP8-bound, occluded state EMDB-47213: Structure of the phosphate exporter XPR1/SLC53A1, Pi and InsP8-bound, inward-open/occluded state EMDB-47214: Structure of the phosphate exporter XPR1/SLC53A1, Pi and InsP8-bound, occluded state |
| 化合物 | ![]() ChemComp-PO4: ![]() ChemComp-CLR: ![]() ChemComp-CPL: ![]() ChemComp-I8P: ![]() ChemComp-HOH: |
| 由来 |
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キーワード | TRANSPORT PROTEIN / Inorganic phosphate exporter |
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