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Structures of human SGLT in the occluded state reveal conformational changes during sugar transport

Author

Listed:
  • Wenhao Cui

    (Beijing Key Laboratory of Cardiometabolic Molecular Medicine
    Peking University)

  • Yange Niu

    (Beijing Key Laboratory of Cardiometabolic Molecular Medicine
    Peking University)

  • Zejian Sun

    (Peking University
    Peking University)

  • Rui Liu

    (Beijing Key Laboratory of Cardiometabolic Molecular Medicine
    Peking University)

  • Lei Chen

    (Beijing Key Laboratory of Cardiometabolic Molecular Medicine
    Peking University
    Peking University)

Abstract

Sodium-Glucose Cotransporters (SGLT) mediate the uphill uptake of extracellular sugars and play fundamental roles in sugar metabolism. Although their structures in inward-open and outward-open conformations are emerging from structural studies, the trajectory of how SGLTs transit from the outward-facing to the inward-facing conformation remains unknown. Here, we present the cryo-EM structures of human SGLT1 and SGLT2 in the substrate-bound state. Both structures show an occluded conformation, with not only the extracellular gate but also the intracellular gate tightly sealed. The sugar substrate are caged inside a cavity surrounded by TM1, TM2, TM3, TM6, TM7, and TM10. Further structural analysis reveals the conformational changes associated with the binding and release of substrates. These structures fill a gap in our understanding of the structural mechanisms of SGLT transporters.

Suggested Citation

  • Wenhao Cui & Yange Niu & Zejian Sun & Rui Liu & Lei Chen, 2023. "Structures of human SGLT in the occluded state reveal conformational changes during sugar transport," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38720-1
    DOI: 10.1038/s41467-023-38720-1
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    References listed on IDEAS

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    1. Yange Niu & Wenhao Cui & Rui Liu & Sanshan Wang & Han Ke & Xiaoguang Lei & Lei Chen, 2022. "Structural mechanism of SGLT1 inhibitors," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    2. Chengcheng Guan & Yange Niu & Si-Cong Chen & Yunlu Kang & Jing-Xiang Wu & Koji Nishi & Catherine C. Y. Chang & Ta-Yuan Chang & Tuoping Luo & Lei Chen, 2020. "Structural insights into the inhibition mechanism of human sterol O-acyltransferase 1 by a competitive inhibitor," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
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    1. Farha Khan & Matthias Elgeti & Samuel Grandfield & Aviv Paz & Fiona B. Naughton & Frank V. Marcoline & Thorsten Althoff & Natalia Ermolova & Ernest M. Wright & Wayne L. Hubbell & Michael Grabe & Jeff , 2023. "Membrane potential accelerates sugar uptake by stabilizing the outward facing conformation of the Na/glucose symporter vSGLT," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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