9WT2

Cryo-EM structure of Pi-free G6PT1 treated with GlcN6P

9WT2 の概要

• エントリーDOI: 10.2210/pdb9wt2/pdb
• 関連するPDBエントリー: 9UGY 9WS8
• EMDBエントリー: 66215
• 分子名称: Glucose-6-phosphate exchanger SLC37A4 (1 entity in total)
• 機能のキーワード: g6p, 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: 92783.62

構造登録者

Shuai, G.,Xia, Y.,Qian, W. (登録日: 2025-09-15, 公開日: 2026-01-07, 最終更新日: 2026-01-14)

主引用文献

Wang, Q.,Guo, N.,Du, Y.,Liu, J.,Ai, W.,Yang, F.,Zhu, Y.,Zhao, Y.,Wu, D.,Liu, L.,Yao, X.,Gao, S.
Structures of human glucose-6-phosphate transporter reveal reciprocal antiport mechanism driving glucose-6-phosphate and inorganic phosphate exchange.
Nat Commun, 16:11441-11441, 2025

PubMed Abstract: 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.

PubMed: 41381426
DOI: 10.1038/s41467-025-66386-4

実験手法

ELECTRON MICROSCOPY (3.12 Å)