8jf0
Human sodium-dependent vitamin C transporter 1 in an intermediate state
Structural highlights
FunctionS23A1_HUMAN Sodium:ascorbate cotransporter. Mediates electrogenic uptake of vitamin C, with a stoichiometry of 2 Na(+) for each ascorbate (PubMed:10556483, PubMed:10556521, PubMed:10631088, PubMed:36749388). Has retained some ancestral activity toward nucleobases such as urate, an oxidized purine. Low-affinity high-capacity sodium:urate cotransporter, may regulate serum urate levels by serving as a renal urate re-absorber (PubMed:36749388).[1] [2] [3] [4] Inactive transporter.[5] Publication Abstract from PubMedVitamin 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 A 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. Dimeric transport mechanism of human vitamin C transporter SVCT1.,Kobayashi TA, Shimada H, Sano FK, Itoh Y, Enoki S, Okada Y, Kusakizako T, Nureki O Nat Commun. 2024 Jul 2;15(1):5569. doi: 10.1038/s41467-024-49899-2. PMID:38956111[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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