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	Structures of human glucose-6-phosphate transporter reveal reciprocal antiport mechanism driving glucose-6-phosphate and inorganic phosphate exchange.
ジャーナル・号・ページ	Nat Commun, Vol. 16, Issue 1, Page 11441, Year 2025
掲載日	2025年12月11日
著者	Qian Wang / Ningjie Guo / Yunxiang Du / Junwu Liu / Wanting Ai / Fengyi Yang / Yuanzai Zhu / Yuanyuan Zhao / Di Wu / Lei Liu / Xia Yao / Shuai Gao /
PubMed 要旨	Glucose-6-phosphate transporter 1 (G6PT1) is essential for systemic glucose homeostasis, and its deficiency causes glycogen storage disease type 1b (GSD1b). G6PT1 functions as a sugar- ...Glucose-6-phosphate transporter 1 (G6PT1) is essential for systemic glucose homeostasis, and its deficiency causes glycogen storage disease type 1b (GSD1b). G6PT1 functions as a sugar-phosphate/inorganic phosphate (Pi) antiporter, orchestrating G6P transport into the endoplasmic reticulum lumen driven by a Pi gradient. Despite its physiological significance, the molecular mechanisms underlying substrate recognition and antiport activity remain poorly characterized. Here, we present cryo-electron microscopy structures of human G6PT1 in apo, Pi-bound, and GlcN6P-bound (a G6P analogue) states, all captured in cytosol-open conformations. Combined with molecular docking and functional assays, these structures elucidate the molecular basis for Pi and G6P recognition in G6PT1. Comparative analysis reveals that Pi binding triggers an interdomain salt bridge formation, resulting in a thicker luminal gate and a more compact central cavity for G6P binding. In addition to the monomer, we identify a dimeric assembly of G6PT1. Mutating key residues at the dimer interface impairs transport activity, suggesting a regulatory role for oligomerization. Our findings thus provide a mechanistic framework for understanding G6PT1 working mechanism and its pathological dysregulation in GSD1b.
リンク	Nat Commun / PubMed:41381426 / PubMed Central
手法	EM (単粒子)
解像度	2.89 - 3.5 Å
構造データ	64144 9ugu EMDB-64144, PDB-9ugu: Cryo-EM Structure of Apo-G6PT1 手法: EM (単粒子) / 解像度: 3.07 Å 64147 9ugx EMDB-64147, PDB-9ugx: Cryo-EM Structure of G6PT1-apo monomer in pi buffer 手法: EM (単粒子) / 解像度: 3.16 Å 64148 9ugy EMDB-64148, PDB-9ugy: Cryo-EM Structure of G6PT1 bound with GlcN6P 手法: EM (単粒子) / 解像度: 3.5 Å 66194 9ws8 EMDB-66194, PDB-9ws8: Cryo-EM Structure of G6PT1 treated with G6P 手法: EM (単粒子) / 解像度: 3.47 Å 66215 9wt2 EMDB-66215, PDB-9wt2: Cryo-EM structure of Pi-free G6PT1 treated with GlcN6P 手法: EM (単粒子) / 解像度: 3.12 Å 66658 9x8x EMDB-66658, PDB-9x8x: Cryo-EM Structure of G6PT1 bound with lower pi 手法: EM (単粒子) / 解像度: 2.89 Å 66660 9x95 EMDB-66660, PDB-9x95: Cryo-EM Structure of G6PT1 without GlcN6P 手法: EM (単粒子) / 解像度: 3.5 Å 66661 9x97 EMDB-66661, PDB-9x97: Cryo-EM Structure of G6PT1 bound with upper pi 手法: EM (単粒子) / 解像度: 2.89 Å
化合物	ChemComp-GLP: 2-amino-2-deoxy-6-O-phosphono-alpha-D-glucopyranose / α-D-グルコサミン6-りん酸 ChemComp-PO4: PHOSPHATE ION / ホスファ-ト
由来	homo sapiens (ヒト)
キーワード	TRANSPORT PROTEIN / G6P