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Dimeric transport mechanism of human vitamin C transporter SVCT1.
Kobayashi, Takaaki A; Shimada, Hiroto; Sano, Fumiya K; Itoh, Yuzuru; Enoki, Sawako; Okada, Yasushi; Kusakizako, Tsukasa; Nureki, Osamu.
Afiliação
  • 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.
  • Sano FK; Research Division, Chugai Pharmaceutical Co., Ltd., Kanagawa, Japan.
  • Itoh Y; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
  • Enoki S; Department of Biological Sciences, 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.
  • Kusakizako T; Department of Physics, and Universal Biology Institute (UBI), Graduate School of Science, The University of Tokyo, Tokyo, Japan.
  • Nureki O; Department of Cell Biology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Nat Commun ; 15(1): 5569, 2024 Jul 02.
Article em En | MEDLINE | ID: mdl-38956111
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ácido Ascórbico / Microscopia Crioeletrônica / Transportadores de Sódio Acoplados à Vitamina C Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ácido Ascórbico / Microscopia Crioeletrônica / Transportadores de Sódio Acoplados à Vitamina C Idioma: En Ano de publicação: 2024 Tipo de documento: Article