National Natural Science Foundation of China (NSFC)
91957201
China
National Natural Science Foundation of China (NSFC)
31821091
China
National Natural Science Foundation of China (NSFC)
31870833
China
Citation
Journal: Nat Commun / Year: 2023 Title: Structures of human SGLT in the occluded state reveal conformational changes during sugar transport. Authors: Wenhao Cui / Yange Niu / Zejian Sun / Rui Liu / Lei Chen / Abstract: 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 ...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.
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