National Natural Science Foundation of China (NSFC)
GG2070000569
中国
Ministry of Science and Technology (MoST, China)
2021YFF0600801
中国
Other government
KY9100000032
Other government
WK2070000183
Other government
WK9100000044
引用
ジャーナル: Nat Commun / 年: 2023 タイトル: Structural basis of vitamin C recognition and transport by mammalian SVCT1 transporter. 著者: Mingxing Wang / Jin He / Shanshan Li / Qianwen Cai / Kaiming Zhang / Ji She / 要旨: 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 (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.