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Structural basis of vitamin C recognition and transport by mammalian SVCT1 transporter

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  • Mingxing Wang

    (University of Science and Technology of China
    University of Science and Technology of China
    University of Science and Technology of China)

  • Jin He

    (University of Science and Technology of China
    University of Science and Technology of China
    University of Science and Technology of China)

  • Shanshan Li

    (University of Science and Technology of China
    University of Science and Technology of China
    University of Science and Technology of China)

  • Qianwen Cai

    (University of Science and Technology of China)

  • Kaiming Zhang

    (University of Science and Technology of China
    University of Science and Technology of China
    University of Science and Technology of China)

  • Ji She

    (University of Science and Technology of China
    University of Science and Technology of China
    University of Science and Technology of China)

Abstract

Vitamin C (L-ascorbic acid) is an essential nutrient for human health, and its deficiency has long been known to cause scurvy. Sodium-dependent vitamin C transporters (SVCTs) are responsible for vitamin C uptake and tissue distribution in mammals. Here, we present cryogenic electron microscopy structures of mouse SVCT1 in both the apo and substrate-bound states. Mouse SVCT1 forms a homodimer with each protomer containing a core domain and a gate domain. The tightly packed extracellular interfaces between the core domain and gate domain stabilize the protein in an inward-open conformation for both the apo and substrate-bound structures. Vitamin C binds at the core domain of each subunit, and two potential sodium ions are identified near the binding site. The coordination of sodium ions by vitamin C explains their coupling transport. SVCTs probably deliver substrate through an elevator mechanism in combination with local structural arrangements. Altogether, our results reveal the molecular mechanism by which SVCTs recognize vitamin C and lay a foundation for further mechanistic studies on SVCT substrate transport.

Suggested Citation

  • Mingxing Wang & Jin He & Shanshan Li & Qianwen Cai & Kaiming Zhang & Ji She, 2023. "Structural basis of vitamin C recognition and transport by mammalian SVCT1 transporter," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37037-3
    DOI: 10.1038/s41467-023-37037-3
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    References listed on IDEAS

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    Cited by:

    1. Takaaki A. Kobayashi & Hiroto Shimada & Fumiya K. Sano & Yuzuru Itoh & Sawako Enoki & Yasushi Okada & Tsukasa Kusakizako & Osamu Nureki, 2024. "Dimeric transport mechanism of human vitamin C transporter SVCT1," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    2. Benedikt T. Kuhn & Jonathan Zöller & Iwan Zimmermann & Tim Gemeinhardt & Dogukan H. Özkul & Julian D. Langer & Markus A. Seeger & Eric R. Geertsma, 2024. "Interdomain-linkers control conformational transitions in the SLC23 elevator transporter UraA," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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