@article{e8bd6debdc0c43b2af163327a714a905,
title = "Cryo-EM structure of human glucose transporter GLUT4",
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 {\AA} 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.",
author = "Yafei Yuan and Fang Kong and Hanwen Xu and Angqi Zhu and Nieng Yan and Chuangye Yan",
note = "Funding Information: We thank Dr. Nan Liu and Dr. Hongwei Wang for providing the graphene grids and Dr. Fan Yang for technical support during EM data collection. We thank the Tsinghua University Branch of China National Center for Protein Sciences (Beijing) for providing the cryo-EM facility support and the computational facility support. This work was funded by the National Key R&D Program of China (2020YFA0509301, C.Y.), Beijing Nova Program (Z201100006820039, C.Y.), Beijing Frontier Research Center for Biological Structure, Beijing Advanced Innovation Center for Structural Biology, and Start-up funds from Tsinghua-Peking Center for Life Sciences and Tsinghua University. Funding Information: We thank Dr. Nan Liu and Dr. Hongwei Wang for providing the graphene grids and Dr. Fan Yang for technical support during EM data collection. We thank the Tsinghua University Branch of China National Center for Protein Sciences (Beijing) for providing the cryo-EM facility support and the computational facility support. This work was funded by the National Key R&D Program of China (2020YFA0509301, C.Y.), Beijing Nova Program (Z201100006820039, C.Y.), Beijing Frontier Research Center for Biological Structure, Beijing Advanced Innovation Center for Structural Biology, and Start-up funds from Tsinghua-Peking Center for Life Sciences and Tsinghua University. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41467-022-30235-5",
language = "English (US)",
volume = "13",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}