Cryo-EM structure of human glucose transporter GLUT4

Yafei Yuan, Fang Kong, Hanwen Xu, Angqi Zhu, Nieng Yan, Chuangye Yan

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


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.

Original languageEnglish (US)
Article number2671
JournalNature communications
Issue number1
StatePublished - Dec 2022

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


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