8JEW

Human sodium-dependent vitamin C transporter 1 bound to L-ascorbic acid in an inward-open state

Summary for 8JEW

• Entry DOI: 10.2210/pdb8jew/pdb
• Related: 8JEZ 8JF0 8JF1
• EMDB information: 36201
• Descriptor: Solute carrier family 23 member 1, ASCORBIC ACID, SODIUM ION, ... (9 entities in total)
• Functional Keywords: transporter, membrane protein, ascorbic acid, vitamin c, sodium, transport protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 69104.20

Authors

Kobayashi, T.A.,Kusakizako, T.,Nureki, O. (deposition date: 2023-05-16, release date: 2024-05-22, Last modification date: 2024-12-04)

Primary citation

Kobayashi, T.A.,Shimada, H.,Sano, F.K.,Itoh, Y.,Enoki, S.,Okada, Y.,Kusakizako, T.,Nureki, O.
Dimeric transport mechanism of human vitamin C transporter SVCT1.
Nat Commun, 15:5569-5569, 2024

PubMed Abstract: Vitamin 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 Å 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.

PubMed: 38956111
DOI: 10.1038/s41467-024-49899-2

Experimental method

ELECTRON MICROSCOPY (2.49 Å)