Structural highlights
Disease[GLUT4_HUMAN] The disease may be caused by variants affecting the gene represented in this entry. Function[GLUT4_HUMAN] Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation. Response to insulin is regulated by its intracellular localization: in the absence of insulin, it is efficiently retained intracellularly within storage compartments in muscle and fat cells. Upon insulin stimulation, translocates from these compartments to the cell surface where it transports glucose from the extracellular milieu into the cell.[UniProtKB:P19357] Publication Abstract from PubMedGLUT4 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 A 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. Cryo-EM structure of human glucose transporter GLUT4.,Yuan Y, Kong F, Xu H, Zhu A, Yan N, Yan C Nat Commun. 2022 May 13;13(1):2671. doi: 10.1038/s41467-022-30235-5. PMID:35562357[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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