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-Structure paper
タイトル | Dimeric transport mechanism of human vitamin C transporter SVCT1. |
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ジャーナル・号・ページ | Nat Commun, Vol. 15, Issue 1, Page 5569, Year 2024 |
掲載日 | 2024年7月2日 |
著者 | Takaaki A Kobayashi / Hiroto Shimada / Fumiya K Sano / Yuzuru Itoh / Sawako Enoki / Yasushi Okada / Tsukasa Kusakizako / Osamu Nureki / |
PubMed 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. |
リンク | Nat Commun / PubMed:38956111 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.49 - 3.5 Å |
構造データ | EMDB-36201, PDB-8jew: EMDB-36204, PDB-8jez: EMDB-36205, PDB-8jf0: EMDB-36206, PDB-8jf1: |
化合物 | ChemComp-ASC: ChemComp-NA: ChemComp-AV0: ChemComp-LBN: ChemComp-CLR: ChemComp-NAG: ChemComp-PLM: ChemComp-HOH: ChemComp-Y01: |
由来 |
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キーワード | TRANSPORT PROTEIN / Transporter / Membrane protein / Ascorbic acid / Vitamin C / Sodium / Solute carrier |