EMD-39230

Single-particle
4.59 Å
EMD-39230 Deposition: 25/02/2024
Map released: 09/10/2024
Last modified: 18/12/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-39230

Cryo EM structure of human phosphate channel XPR1 at intermediate state

EMD-39230

Single-particle
4.59 Å
EMD-39230 Deposition: 25/02/2024
Map released: 09/10/2024
Last modified: 18/12/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: Cryo EM structure of human phosphate channel XPR1 at intermediate state
Fitted models: 8yfu (Avg. Q-score: 0.259)

Deposition Authors: Lu Y , Yue C, Zhang L , Yao D , Yu Y , Cao Y
Structural basis for inositol pyrophosphate gating of the phosphate channel XPR1.
Lu Y , Yue CX , Zhang L , Yao D , Xia Y , Zhang Q , Zhang X , Li S, Shen Y, Cao M, Guo CR , Qin A , Zhao J , Zhou L , Yu Y , Cao Y
(2024) Science , 386 , eadp3252 - eadp3252
PUBMED: 39325866
DOI: doi:10.1126/science.adp3252
ISSN: 1095-9203
ASTM: SCIEAS
Abstract:
Precise regulation of intracellular phosphate (Pi) is critical for cellular function, with xenotropic and polytropic retrovirus receptor 1 (XPR1) serving as the sole Pi exporter in humans. The mechanism of Pi efflux, activated by inositol pyrophosphates (PP-IPs), has remained unclear. This study presents cryo-electron microscopy structures of XPR1 in multiple conformations, revealing a transmembrane pathway for Pi export and a dual-binding activation pattern for PP-IPs. A canonical binding site is located at the dimeric interface of Syg1/Pho81/XPR1 (SPX) domains, and a second site, biased toward PP-IPs, is found between the transmembrane and SPX domains. By integrating structural studies with electrophysiological analyses, we characterized XPR1 as an inositol phosphates (IPs)/PP-IPs-activated phosphate channel. The interplay among its transmembrane domains, SPX domains, and IPs/PP-IPs orchestrates the conformational transition between its closed and open states.