30uv | pdb_000030uv
Structure of NaCT in Choline Chloride
Structural highlights
DiseaseS13A5_HUMAN Undetermined early-onset epileptic encephalopathy;Amelocerebrohypohidrotic syndrome;Pyridoxine-dependent epilepsy. The disease is caused by variants affecting the gene represented in this entry. FunctionS13A5_HUMAN High-affinity sodium/citrate cotransporter that mediates citrate entry into cells. The transport process is electrogenic; it is the trivalent form of citrate rather than the divalent form that is recognized as a substrate. May facilitate the utilization of circulating citrate for the generation of metabolic energy and for the synthesis of fatty acids and cholesterol.[1] [2] Publication Abstract from PubMedThe human sodium-citrate cotransporter NaCT imports various tri- and dicarboxylates into the cell as TCA cycle intermediates. This substrate uptake process is driven by an inward sodium gradient. The protein is a member of the Divalent Anion-Sodium Symporter (DASS) family. Whereas extensive biochemical and structural studies have been carried out for NaCT, how the substrate binding and translocation is coupled to the sodium gradient remains unclear. Here using single particle cryo-electron microscopy, we determined the structures of the human NaCT protein in three states: sodium-free, in the presence of sodium, and sodium- and substrate-bound. These structures suggest a simultaneous binding mechanism for sodium-substrate coupling, distinct from the sequential binding, conformational selection mechanism previously observed for the bacterial DASS protein VcINDY. Structures of the human sodium-citrate cotransporter NaCT with and without substrates.,Sauer DB, Song J, Marden JJ, Wang B, Sowerby K, Sudar JC, Rice WJ, Wang DN bioRxiv [Preprint]. 2026 Jul 12:2026.07.08.737274. doi: , 10.64898/2026.07.08.737274. PMID:42465234[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
