Dimeric transport mechanism of human vitamin C transporter SVCT1.

Autor: Kobayashi TA; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan., Shimada H; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.; Research Division, Chugai Pharmaceutical Co., Ltd., Kanagawa, Japan., Sano FK; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan., Itoh Y; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan., Enoki S; Department of Physics, and Universal Biology Institute (UBI), Graduate School of Science, The University of Tokyo, Tokyo, Japan., Okada Y; Department of Physics, and Universal Biology Institute (UBI), Graduate School of Science, The University of Tokyo, Tokyo, Japan.; Department of Cell Biology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.; Laboratory for Cell Polarity Regulation, RIKEN Center for Biosystems Dynamics Research (BDR), Osaka, Japan.; International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo, Tokyo, Japan., Kusakizako T; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan. kusakizako@bs.s.u-tokyo.ac.jp., Nureki O; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan. nureki@bs.s.u-tokyo.ac.jp.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jul 02; Vol. 15 (1), pp. 5569. Date of Electronic Publication: 2024 Jul 02.
DOI: 10.1038/s41467-024-49899-2
Abstrakt: 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).)
Databáze: MEDLINE
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