8YFD

Cryo EM structure of human phosphate channel XPR1 at open state

8YFD の概要

• エントリーDOI: 10.2210/pdb8yfd/pdb
• EMDBエントリー: 39220
• 分子名称: Solute carrier family 53 member 1 (1 entity in total)
• 機能のキーワード: phosphate channel, membrane protein, phosphate homeostasis, transport protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 92938.38

構造登録者

Lu, Y.,Yue, C.,Zhang, L.,Yao, D.,Yu, Y.,Cao, Y. (登録日: 2024-02-24, 公開日: 2024-10-09, 最終更新日: 2025-07-16)

主引用文献

Lu, Y.,Yue, C.X.,Zhang, L.,Yao, D.,Xia, Y.,Zhang, Q.,Zhang, X.,Li, S.,Shen, Y.,Cao, M.,Guo, C.R.,Qin, A.,Zhao, J.,Zhou, L.,Yu, Y.,Cao, Y.
Structural basis for inositol pyrophosphate gating of the phosphate channel XPR1.
Science, 386:eadp3252-eadp3252, 2024

PubMed 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.

PubMed: 39325866
DOI: 10.1126/science.adp3252

実験手法

ELECTRON MICROSCOPY (3.57 Å)