Dimeric transport mechanism of human vitamin C transporter SVCT1.

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. © 2024. The Author(s).

Citation

Takaaki A Kobayashi, Hiroto Shimada, Fumiya K Sano, Yuzuru Itoh, Sawako Enoki, Yasushi Okada, Tsukasa Kusakizako, Osamu Nureki. Dimeric transport mechanism of human vitamin C transporter SVCT1. Nature communications. 2024 Jul 02;15(1):5569

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PMID: 38956111

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