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TitleStructural basis of vitamin C recognition and transport by mammalian SVCT1 transporter.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 1361, Year 2023
Publish dateMar 13, 2023
AuthorsMingxing Wang / Jin He / Shanshan Li / Qianwen Cai / Kaiming Zhang / Ji She /
PubMed AbstractVitamin 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 (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.
External linksNat Commun / PubMed:36914666 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 3.5 Å
Structure data

34094

7ytw

EMDB-34094, PDB-7ytw:
Structural basis of vitamin C recognition and transport by mammalian SVCT1 transporter
Method: EM (single particle) / Resolution: 3.2 Å

34095

7yty

EMDB-34095, PDB-7yty:
Mouse SVCT1 in an apo state
Method: EM (single particle) / Resolution: 3.5 Å

Chemicals

ChemComp-NA:
Unknown entry

ChemComp-ASC:
ASCORBIC ACID / medication*YM / Vitamin C

ChemComp-HOH:
WATER / Water

Source
  • mus musculus (house mouse)
KeywordsSTRUCTURAL PROTEIN / transporter / membrane protein / Vitamin C / sodium

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