9KVV

Cryo-EM structure of human G6PT in complex with G6P

9KVV の概要

• エントリーDOI: 10.2210/pdb9kvv/pdb
• EMDBエントリー: 62602
• 分子名称: Glucose-6-phosphate exchanger SLC37A4, 6-O-phosphono-beta-D-glucopyranose (2 entities in total)
• 機能のキーワード: g6pt, cryo-em, g6p, transport protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 46651.94

構造登録者

Jiang, D.H.,Xia, Z.Y. (登録日: 2024-12-05, 公開日: 2025-11-12)

主引用文献

Xia, Z.,Wang, Y.,Wu, D.,Chi, C.,Li, C.,Chen, L.,Jiang, D.
Structural basis for transport and inhibition of the human glucose-6-phosphate transporter G6PT.
Nat Commun, 16:9420-9420, 2025

PubMed Abstract: The human glucose-6-phosphate transporter (G6PT) moves glucose-6-phosphate (G6P) into the lumen of endoplasmic reticulum, playing a vital role in glucose homeostasis. Dysregulation of G6PT causes glycogen storage disease 1b. Despite its functional importance, the structure, G6P recognition, and inhibition mechanism of G6PT remain unclear. Here, we report the cryo-EM structures of human G6PT in apo, G6P-bound, and the specific inhibitor chlorogenic acid (CHA)-bound forms, elucidating the structural basis for G6PT transport and inhibition. The G6P pocket comprises subsite A for phosphate and subsite B for glucose. The CHA occupies the G6P site and locks G6PT in a partly-occluded state. Functional assays demonstrate that G6PT activity is enhanced by co-expression of glucose-6-phosphatase (G6PC), but G6PT does not form a complex with G6PC. Together, this study provides a solid foundation for understanding the structure‒function relationships and pathology of G6PT and sheds light on the future development of potential therapeutics targeting G6PT.

PubMed: 41136424
DOI: 10.1038/s41467-025-64464-1

実験手法

ELECTRON MICROSCOPY (3.6 Å)