8y5w
human NaS1 intermediate state 2
Structural highlights
FunctionS13A1_HUMAN Sodium:sulfate symporter that mediates sulfate reabsorption in the kidney and small intestine (PubMed:11161786). Can also mediate the transport of selenate and thiosulfate (By similarity).[UniProtKB:Q07782][1] Publication Abstract from PubMedSulfate (SO(4)(2-)) is a pivotal inorganic anion with essential roles in mammalian physiology. NaS1, a member of solute carrier 13 family and divalent anion/sodium symporter family, functions as a Na(+)-sulfate cotransporter, facilitating sulfate (re)absorption across renal proximal tubule and small intestine epithelia. While previous studies have linked several human disorders to mutations in the NaS1 gene, its transport mechanism remains unclear. Here, we report the cryo-electron microscopy structures of five distinct conformations of the human NaS1 at resolutions of 2.7 to 3.3 angstroms, revealing the substrates recognition mechanism and the conformational change of NaS1 during the Na(+)-sulfate cotransport cycle. Our studies delineate the molecular basis of the detailed dynamic transport cycle of NaS1. These findings advance the current understanding of the Na(+)-sulfate cotransport mechanism, human sulfate (re)absorption, and the implications of disease-associated NaS1 mutations. Structural basis for the reaction cycle and transport mechanism of human Na(+)-sulfate cotransporter NaS1 (SLC13A1).,Chen X, Zhang Y, Yin J, Liu C, Xie M, Wang Y, Chen M, Zhang R, Yuan X, Li D, Chen X, Gao X, Cai G, Zhang S, Zhou B, Yang M Sci Adv. 2024 Nov 22;10(47):eado6778. doi: 10.1126/sciadv.ado6778. Epub 2024 Nov , 22. PMID:39576865[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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