Structural highlights
Disease
SC5A2_HUMAN Familial renal glucosuria. The disease is caused by variants affecting the gene represented in this entry.
Function
SC5A2_HUMAN Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose at the plasma membrane, with a Na(+) to sugar coupling ratio of 1:1. Transporter activity is driven by a transmembrane Na(+) electrochemical gradient set by the Na(+)/K(+) pump (PubMed:20980548, PubMed:28592437, PubMed:34880493). Has a primary role in D-glucose reabsorption from glomerular filtrate across the brush border of the early proximal tubules of the kidney (By similarity).[UniProtKB:Q923I7][1] [2] [3]
Publication Abstract from PubMed
Sodium-Glucose Cotransporters (SGLT) mediate the uphill uptake of extracellular sugars and play fundamental roles in sugar metabolism. Although their structures in inward-open and outward-open conformations are emerging from structural studies, the trajectory of how SGLTs transit from the outward-facing to the inward-facing conformation remains unknown. Here, we present the cryo-EM structures of human SGLT1 and SGLT2 in the substrate-bound state. Both structures show an occluded conformation, with not only the extracellular gate but also the intracellular gate tightly sealed. The sugar substrate are caged inside a cavity surrounded by TM1, TM2, TM3, TM6, TM7, and TM10. Further structural analysis reveals the conformational changes associated with the binding and release of substrates. These structures fill a gap in our understanding of the structural mechanisms of SGLT transporters.
Structures of human SGLT in the occluded state reveal conformational changes during sugar transport.,Cui W, Niu Y, Sun Z, Liu R, Chen L Nat Commun. 2023 May 22;14(1):2920. doi: 10.1038/s41467-023-38720-1. PMID:37217492[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hummel CS, Lu C, Loo DD, Hirayama BA, Voss AA, Wright EM. Glucose transport by human renal Na+/D-glucose cotransporters SGLT1 and SGLT2. Am J Physiol Cell Physiol. 2011 Jan;300(1):C14-21. doi:, 10.1152/ajpcell.00388.2010. Epub 2010 Oct 27. PMID:20980548 doi:http://dx.doi.org/10.1152/ajpcell.00388.2010
- ↑ Coady MJ, Wallendorff B, Lapointe JY. Characterization of the transport activity of SGLT2/MAP17, the renal low-affinity Na(+)-glucose cotransporter. Am J Physiol Renal Physiol. 2017 Aug 1;313(2):F467-F474. PMID:28592437 doi:10.1152/ajprenal.00628.2016
- ↑ Niu Y, Liu R, Guan C, Zhang Y, Chen Z, Hoerer S, Nar H, Chen L. Structural basis of inhibition of the human SGLT2-MAP17 glucose transporter. Nature. 2022 Jan;601(7892):280-284. PMID:34880493 doi:10.1038/s41586-021-04212-9
- ↑ Cui W, Niu Y, Sun Z, Liu R, Chen L. Structures of human SGLT in the occluded state reveal conformational changes during sugar transport. Nat Commun. 2023 May 22;14(1):2920. PMID:37217492 doi:10.1038/s41467-023-38720-1
