Dimeric transport mechanism of human vitamin C transporter SVCT1.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 Jul 2024
02 Jul 2024
Historique:
received:
31
05
2023
accepted:
20
06
2024
medline:
3
7
2024
pubmed:
3
7
2024
entrez:
2
7
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38956111
doi: 10.1038/s41467-024-49899-2
pii: 10.1038/s41467-024-49899-2
doi:
Substances chimiques
Sodium-Coupled Vitamin C Transporters
0
Ascorbic Acid
PQ6CK8PD0R
SLC23A1 protein, human
0
Sodium
9NEZ333N27
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5569Subventions
Organisme : MEXT | Japan Science and Technology Agency (JST)
ID : 20344981
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP23ama121002
Informations de copyright
© 2024. The Author(s).
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