7sla
CryoEM structure of SGLT1 at 3.15 Angstrom resolution
Structural highlights
DiseaseSC5A1_HUMAN Glucose-galactose malabsorption. The disease is caused by variants affecting the gene represented in this entry. FunctionSC5A1_HUMAN Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose or D-galactose at the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1. Transporter activity is driven by a transmembrane Na(+) electrochemical gradient set by the Na(+)/K(+) pump (PubMed:20980548, PubMed:34880492, PubMed:35077764, PubMed:8563765). Has a primary role in the transport of dietary monosaccharides from enterocytes to blood. Responsible for the absorption of D-glucose or D-galactose across the apical brush-border membrane of enterocytes, whereas basolateral exit is provided by GLUT2. Additionally, functions as a D-glucose sensor in enteroendocrine cells, triggering the secretion of the incretins GCG and GIP that control food intake and energy homeostasis (By similarity) (PubMed:8563765). Together with SGLT2, functions in reabsorption of D-glucose from glomerular filtrate, playing a nonredundant role in the S3 segment of the proximal tubules (By similarity). Transports D-glucose into endometrial epithelial cells, controlling glycogen synthesis and nutritional support for the embryo as well as the decidual transformation of endometrium prior to conception (PubMed:28974690). Acts as a water channel enabling passive water transport across the plasma membrane in response to the osmotic gradient created upon sugar and Na(+) uptake. Has high water conductivity, comparable to aquaporins, and therefore is expected to play an important role in transepithelial water permeability, especially in the small intestine.[UniProtKB:Q8C3K6][1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedGlucose is a primary energy source in living cells. The discovery in 1960s that a sodium gradient powers the active uptake of glucose in the intestine(1) heralded the concept of a secondary active transporter that can catalyse the movement of a substrate against an electrochemical gradient by harnessing energy from another coupled substrate. Subsequently, coupled Na(+)/glucose transport was found to be mediated by sodium-glucose cotransporters(2,3) (SGLTs). SGLTs are responsible for active glucose and galactose absorption in the intestine and for glucose reabsorption in the kidney(4), and are targeted by multiple drugs to treat diabetes(5). Several members within the SGLT family transport key metabolites other than glucose(2). Here we report cryo-electron microscopy structures of the prototypic human SGLT1 and a related monocarboxylate transporter SMCT1 from the same family. The structures, together with molecular dynamics simulations and functional studies, define the architecture of SGLTs, uncover the mechanism of substrate binding and selectivity, and shed light on water permeability of SGLT1. These results provide insights into the multifaceted functions of SGLTs. Structure and mechanism of the SGLT family of glucose transporters.,Han L, Qu Q, Aydin D, Panova O, Robertson MJ, Xu Y, Dror RO, Skiniotis G, Feng L Nature. 2022 Jan;601(7892):274-279. doi: 10.1038/s41586-021-04211-w. Epub 2021 , Dec 8. PMID:34880492[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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