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Dimeric transport mechanism of human vitamin C transporter SVCT1

Author

Listed:
  • Takaaki A. Kobayashi

    (The University of Tokyo)

  • Hiroto Shimada

    (The University of Tokyo
    Chugai Pharmaceutical Co., Ltd.)

  • Fumiya K. Sano

    (The University of Tokyo)

  • Yuzuru Itoh

    (The University of Tokyo)

  • Sawako Enoki

    (The University of Tokyo)

  • Yasushi Okada

    (The University of Tokyo
    The University of Tokyo
    RIKEN Center for Biosystems Dynamics Research (BDR)
    The University of Tokyo)

  • Tsukasa Kusakizako

    (The University of Tokyo)

  • Osamu Nureki

    (The University of Tokyo)

Abstract

Vitamin C plays important roles as a cofactor in many enzymatic reactions and as an antioxidant against oxidative stress. As some mammals including humans cannot synthesize vitamin C de novo from glucose, its uptake from dietary sources is essential, and is mediated by the sodium-dependent vitamin C transporter 1 (SVCT1). Despite its physiological significance in maintaining vitamin C homeostasis, the structural basis of the substrate transport mechanism remained unclear. Here, we report the cryo-EM structures of human SVCT1 in different states at 2.5–3.5 Å resolutions. The binding manner of vitamin C together with two sodium ions reveals the counter ion-dependent substrate recognition mechanism. Furthermore, comparisons of the inward-open and occluded structures support a transport mechanism combining elevator and distinct rotational motions. Our results demonstrate the molecular mechanism of vitamin C transport with its underlying conformational cycle, potentially leading to future industrial and medical applications.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49899-2
    DOI: 10.1038/s41467-024-49899-2
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