EMD-39230
Cryo EM structure of human phosphate channel XPR1 at intermediate state
EMD-39230
Single-particle4.59 Å
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Map released: 09/10/2024
Last modified: 18/12/2024
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
Sample: Cryo EM structure of human phosphate channel XPR1 at intermediate state
Fitted models: 8yfu (Avg. Q-score: 0.259)
Deposition Authors: Lu Y
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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
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(2024) Science , 386 , eadp3252 - eadp3252
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.
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.