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Cryo-EM structure of human glucose transporter GLUT4

Author

Listed:
  • Yafei Yuan

    (Tsinghua University)

  • Fang Kong

    (Tsinghua University)

  • Hanwen Xu

    (Tsinghua University)

  • Angqi Zhu

    (Tsinghua University)

  • Nieng Yan

    (Tsinghua University
    Princeton University)

  • Chuangye Yan

    (Tsinghua University)

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.

Suggested Citation

  • Yafei Yuan & Fang Kong & Hanwen Xu & Angqi Zhu & Nieng Yan & Chuangye Yan, 2022. "Cryo-EM structure of human glucose transporter GLUT4," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30235-5
    DOI: 10.1038/s41467-022-30235-5
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    1. Yuqi Qin & Daqi Yu & Dan Wu & Jiangqing Dong & William Thomas Li & Chang Ye & Kai Chit Cheung & Yingyi Zhang & Yun Xu & YongQiang Wang & Yun Stone Shi & Shangyu Dang, 2023. "Cryo-EM structure of TMEM63C suggests it functions as a monomer," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    2. Albert Suades & Aziz Qureshi & Sarah E. McComas & Mathieu Coinçon & Axel Rudling & Yurie Chatzikyriakidou & Michael Landreh & Jens Carlsson & David Drew, 2023. "Establishing mammalian GLUT kinetics and lipid composition influences in a reconstituted-liposome system," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Yi C. Zeng & Meghna Sobti & Ada Quinn & Nicola J. Smith & Simon H. J. Brown & Jamie I. Vandenberg & Renae M. Ryan & Megan L. O’Mara & Alastair G. Stewart, 2023. "Structural basis of promiscuous substrate transport by Organic Cation Transporter 1," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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