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- Title
Dimeric transport mechanism of human vitamin C transporter SVCT1.
- Authors
Kobayashi, Takaaki A.; Shimada, Hiroto; Sano, Fumiya K.; Itoh, Yuzuru; Enoki, Sawako; Okada, Yasushi; Kusakizako, Tsukasa; Nureki, Osamu
- 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. Vitamin C is an essential nutrient for our daily life, but how it is transported into our bodies remained unclear. Here, authors revealed multiple structures of human vitamin C transporter, providing insights into its molecular mechanisms.
- Subjects
VITAMIN C; ESSENTIAL nutrients; ROTATIONAL motion; SODIUM ions; COUNTER-ions; HOMEOSTASIS
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-49899-2