7WSN

Cryo-EM structure of human glucose transporter GLUT4 bound to cytochalasin B in detergent micelles

7WSN の概要

• エントリーDOI: 10.2210/pdb7wsn/pdb
• 関連するPDBエントリー: 7WSM
• EMDBエントリー: 32760 32761
• 分子名称: Solute carrier family 2, facilitated glucose transporter member 4, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, Cytochalasin B (3 entities in total)
• 機能のキーワード: glucose transporter, glut4, diabetes, cytochalasin b, 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: 57012.21

構造登録者

Yuan, Y.,Kong, F.,Xu, H.,Zhu, A.,Yan, N.,Yan, C. (登録日: 2022-01-30, 公開日: 2022-05-18, 最終更新日: 2025-06-18)

主引用文献

Yuan, Y.,Kong, F.,Xu, H.,Zhu, A.,Yan, N.,Yan, C.
Cryo-EM structure of human glucose transporter GLUT4.
Nat Commun, 13:2671-2671, 2022

PubMed Abstract: GLUT4 is the primary glucose transporter in adipose and skeletal muscle tissues. Its cellular trafficking is regulated by insulin signaling. Failed or reduced plasma membrane localization of GLUT4 is associated with diabetes. Here, we report the cryo-EM structures of human GLUT4 bound to a small molecule inhibitor cytochalasin B (CCB) at resolutions of 3.3 Å in both detergent micelles and lipid nanodiscs. CCB-bound GLUT4 exhibits an inward-open conformation. Despite the nearly identical conformation of the transmembrane domain to GLUT1, the cryo-EM structure reveals an extracellular glycosylation site and an intracellular helix that is invisible in the crystal structure of GLUT1. The structural study presented here lays the foundation for further mechanistic investigation of the modulation of GLUT4 trafficking. Our methods for cryo-EM analysis of GLUT4 will also facilitate structural determination of many other small size solute carriers.

PubMed: 35562357
DOI: 10.1038/s41467-022-30235-5

実験手法

ELECTRON MICROSCOPY (3.31 Å)