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@article{Woubshete:2024:10.1016/j.bbamem.2024.184390,
author = {Woubshete, M and Chan, LI and Diallinas, G and Byrne, B},
doi = {10.1016/j.bbamem.2024.184390},
journal = {Biochim Biophys Acta Biomembr},
title = {The dimer of human SVCT1 is key for transport function.},
url = {http://dx.doi.org/10.1016/j.bbamem.2024.184390},
volume = {1866},
year = {2024}
}
TY - JOUR
AB - Humans and other primates lack the ability to synthesize the essential nutrient, Vitamin C, which is derived exclusively from the diet. Crucial for effective vitamin C uptake are the Na+ dependent Vitamin C transporters, SVCT1 and SVCT2, members of the nucleobase ascorbate transporter (NAT) family. SVCT1 and 2 actively transport the reduced form of Vitamin C, ascorbic acid, into key tissues. The recent structure of the mouse SVCT1 revealed the molecular basis of substrate binding and that, like the other structurally characterised members of the NAT family, it exists as a closely associated dimer. SVCT1 is likely to function via the elevator mechanism with the core domain of each protomer able to bind substrate and move through the membrane carrying the substrate across the membrane. Here we explored the function of a range of variants of the human SVCT1, revealing a range of residues involved in substrate selection and binding, and confirming the importance of the C-terminus in membrane localisation. Furthermore, using a dominant negative mutant we show that the dimer is essential for transport function, as previously seen in the fungal homologue, UapA. In addition, we show that a localisation deficient C-terminal truncation of SVCT1 blocks correct localisation of co-expressed, associated wildtype SVCT1. These results clearly show the importance of the dimer in both correct SVCT1 trafficking and transport activity.
AU - Woubshete,M
AU - Chan,LI
AU - Diallinas,G
AU - Byrne,B
DO - 10.1016/j.bbamem.2024.184390
PY - 2024///
TI - The dimer of human SVCT1 is key for transport function.
T2 - Biochim Biophys Acta Biomembr
UR - http://dx.doi.org/10.1016/j.bbamem.2024.184390
UR - https://www.ncbi.nlm.nih.gov/pubmed/39369805
VL - 1866
ER -
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