Structural basis of vitamin C recognition and transport by mammalian SVCT1 transporter

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.

Endohedral metallofullerene molecular nanomagnets

“…258 On the other hand, gas adsorption can be detected when a pyrene-based covalent organic framework (Py-COF) is introduced as the host. 259 By embedding DySc 2 N@C 80 SMM into the pores of MOF-177, it is demonstrated that the QTM effect at zero field can be effectively suppressed upon encapsulation. 260 A similar observation was also found for the same EMF incorporated into a different MOF structure, which is due to the dilution effect that weakens intermolecular interactions.…”

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