ジャーナル: Nat Commun / 年: 2024 タイトル: Dimeric transport mechanism of human vitamin C transporter SVCT1. 著者: Takaaki A Kobayashi / Hiroto Shimada / Fumiya K Sano / Yuzuru Itoh / Sawako Enoki / Yasushi Okada / Tsukasa Kusakizako / Osamu Nureki / 要旨: 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 ...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.
解像度: 3.5→106.24 Å / Cor.coef. Fo:Fc: 0.838 / SU B: 34.105 / SU ML: 0.54 / ESU R: 0.529 立体化学のターゲット値: MAXIMUM LIKELIHOOD WITH PHASES 詳細: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS