Structural basis of vitamin C recognition and transport by mammalian SVCT1 transporter.
Nat Commun
; 14(1): 1361, 2023 03 13.
Article
em En
| MEDLINE
| ID: mdl-36914666
ABSTRACT
Vitamin C (L-ascorbic acid) is an essential nutrient for human health, and its deficiency has long been known to cause scurvy. Sodium-dependent vitamin C transporters (SVCTs) are responsible for vitamin C uptake and tissue distribution in mammals. Here, we present cryogenic electron microscopy structures of mouse SVCT1 in both the apo and substrate-bound states. Mouse SVCT1 forms a homodimer with each protomer containing a core domain and a gate domain. The tightly packed extracellular interfaces between the core domain and gate domain stabilize the protein in an inward-open conformation for both the apo and substrate-bound structures. Vitamin C binds at the core domain of each subunit, and two potential sodium ions are identified near the binding site. The coordination of sodium ions by vitamin C explains their coupling transport. SVCTs probably deliver substrate through an elevator mechanism in combination with local structural arrangements. Altogether, our results reveal the molecular mechanism by which SVCTs recognize vitamin C and lay a foundation for further mechanistic studies on SVCT substrate transport.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ácido Ascórbico
/
Simportadores
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Transportadores de Sódio Acoplados à Vitamina C
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article