EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Synergistic activation of the human phosphate exporter XPR1 by KIDINS220 and inositol pyrophosphate.
ジャーナル・号・ページ	Nat Commun, Vol. 16, Issue 1, Page 2879, Year 2025
掲載日	2025年3月24日
著者	Peng Zuo / Weize Wang / Zonglin Dai / Jiye Zheng / Shang Yu / Guangxi Wang / Yue Yin / Ling Liang / Yuxin Yin /
PubMed 要旨	Inorganic phosphate (Pi) is essential for life, and its intracellular levels must be tightly regulated to avoid toxicity. XPR1, the sole known phosphate exporter, is critical for maintaining this ...Inorganic phosphate (Pi) is essential for life, and its intracellular levels must be tightly regulated to avoid toxicity. XPR1, the sole known phosphate exporter, is critical for maintaining this balance. Here we report cryo-EM structures of the human XPR1-KIDINS220 complex in substrate-free closed and substrate-bound outward-open states, as well as an XPR1 mutant in a substrate-bound inward-facing state. In the presence of inositol hexaphosphate (InsP) and phosphate, the complex adopts an outward-open conformation, with InsP binding the SPX domain and juxtamembrane regions, indicating active phosphate export. Without phosphate or InsP, the complex closes, with transmembrane helix 9 blocking the outward cavity and a C-terminal loop obstructing the intracellular cavity. XPR1 alone remains closed even with phosphate and InsP. Functional mutagenesis shows that InsP, whose levels vary with Pi availability, works with KIDINS220 to regulate XPR1 activity. These insights into phosphate regulation may aid in developing therapies for ovarian cancer.
リンク	Nat Commun / PubMed:40128258 / PubMed Central
手法	EM (単粒子)
解像度	3.03 - 3.8 Å
構造データ	60704 9ine EMDB-60704, PDB-9ine: Cryo-EM structure of human XPR1 in closed state in the presence of KIDINS220-1-432 手法: EM (単粒子) / 解像度: 3.32 Å 60705 9inf EMDB-60705, PDB-9inf: Cryo-EM structure of human XPR1 in closed state in the presence of KIDINS220-1-432 and 10 mM KH2PO4 手法: EM (単粒子) / 解像度: 3.36 Å 60707 9inh EMDB-60707, PDB-9inh: Cryo-EM structure of human XPR1 in complex with InsP6 in outward-facing state (SPX visible)-in the presence of KIDINS220-1-432 and 10 mM KH2PO4 手法: EM (単粒子) / 解像度: 3.68 Å 60861 9itg EMDB-60861, PDB-9itg: Cryo-EM structure of human XPR1-E622A/F623A mutant in complex with InsP6 in inward-facing state in the presence of 10 mM KH2PO4 手法: EM (単粒子) / 解像度: 3.03 Å 60897 9iuc EMDB-60897, PDB-9iuc: Cryo-EM structure of human XPR1 in complex with InsP6 in closed state - in the presence of KIDINS220-1-432 without substrate KH2PO4 手法: EM (単粒子) / 解像度: 3.8 Å
化合物	ChemComp-CLR: CHOLESTEROL / コレステロ-ル ChemComp-3PE: 1,2-Distearoyl-sn-glycerophosphoethanolamine / DSPE / リン脂質YM ChemComp-LPE: 1-O-OCTADECYL-SN-GLYCERO-3-PHOSPHOCHOLINE / [O-(1-O-オクタデシル-L-グリセロ-3-ホスホ)コリン]アニオン ChemComp-PLM: PALMITIC ACID / パルミチン酸 ChemComp-ACD: ARACHIDONIC ACID / アラキドン酸 ChemComp-HOH: WATER ChemComp-IHP: INOSITOL HEXAKISPHOSPHATE / myo-イノシト-ル六りん酸 ChemComp-PO4: PHOSPHATE ION / ホスファ-ト ChemComp-Y01: CHOLESTEROL HEMISUCCINATE / コレステリルヘミスクシナ-ト ChemComp-1T9*: (2S,3R,4E)-3-hydroxy-2-(octanoylamino)octadec-4-en-1-yl dihydrogen phosphate / N-[(1S,2R,3E)-1-[(ホスホノオキシ)メチル]-2-ヒドロキシ-3-ヘプタデセニル]オクタンアミド
由来	homo sapiens (ヒト)
キーワード	MEMBRANE PROTEIN / SLC53A1 / transporter / phosphate