EMD-38065

Single-particle
2.84 Å
EMD-38065 Deposition: 16/11/2023
Map released: 03/07/2024
Last modified: 09/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-38065

Cryo-EM structures of human XPR1 in closed states

EMD-38065

Single-particle
2.84 Å
EMD-38065 Deposition: 16/11/2023
Map released: 03/07/2024
Last modified: 09/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: transport
Fitted models: 8x5b (Avg. Q-score: 0.575)

Deposition Authors: Jiang DH , Yan R
Human XPR1 structures reveal phosphate export mechanism.
Yan R, Chen H, Liu C, Zhao J , Wu D , Jiang J , Gong J , Jiang D
(2024) Nature , 633 , 960 - 967
PUBMED: 39169184
DOI: doi:10.1038/s41586-024-07852-9
ISSN: 1476-4687
ASTM: NATUAS
Abstract:
Inorganic phosphate (Pi) is a fundamental macronutrient for all living organisms, the homeostasis of which is critical for numerous biological activities1-3. As the only known human Pi exporter to date, XPR1 has an indispensable role in cellular Pi homeostasis4,5. Dysfunction of XPR1 is associated with neurodegenerative disease6-8. However, the mechanisms underpinning XPR1-mediated Pi efflux and regulation by the intracellular inositol polyphosphate (InsPP) sensor SPX domain remain poorly understood. Here we present cryo-electron microscopy structures of human XPR1 in Pi-bound closed, open and InsP6-bound forms, revealing the structural basis for XPR1 gating and regulation by InsPPs. XPR1 consists of an N-terminal SPX domain, a dimer-formation core domain and a Pi transport domain. Within the transport domain, three basic clusters are responsible for Pi binding and transport, and a conserved W573 acts as a molecular switch for gating. In addition, the SPX domain binds to InsP6 and facilitates Pi efflux by liberating the C-terminal loop that limits Pi entry. This study provides a conceptual framework for the mechanistic understanding of Pi homeostasis by XPR1 homologues in fungi, plants and animals.