Dimeric transport mechanism of human vitamin C transporter SVCT1.
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ácido Ascórbico
/
Microscopia Crioeletrônica
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Transportadores de Sódio Acoplados à Vitamina C
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article