Cryo-EM structure of human glucose transporter GLUT4.

TitleCryo-EM structure of human glucose transporter GLUT4.
Publication TypeJournal Article
Year of Publication2022
AuthorsYuan, Y, Kong, F, Xu, H, Zhu, A, Yan, N, Yan, C
JournalNat Commun
Volume13
Issue1
Pagination2671
Date Published2022 05 13
ISSN2041-1723
KeywordsCryoelectron Microscopy, Cytochalasin B, Glucose, Glucose Transport Proteins, Facilitative, Glucose Transporter Type 1, Glucose Transporter Type 4, Humans, Insulin
Abstract

<p>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.</p>

DOI10.1038/s41467-022-30235-5
Alternate JournalNat Commun
PubMed ID35562357
PubMed Central IDPMC9106701
Grant List2020YFA0509301 / / Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology) /
Z201100006820039 / / Beijing Nova Program /