Sodium/glucose transporters (SGLTs) are integral membrane proteins that couple active glucose uptake to the transmembrane sodium gradient, a process central to glucose homeostasis. The bacterial homolog vSGLT from Vibrio parahaemolyticus has provided critical structural and mechanistic insight into transport by this family. Here, we present the first fully open outward-facing structure of any SGLT, captured using a gating-charge mutant K471E identified in a prior mutagenesis study. All-atom molecular dynamics simulations were performed to probe the initial stages of Na + and sugar binding. We captured several spontaneous galactose binding events into the sugar binding pocket and discuss the stability of these binding events related to the presence or absence of Na + in the Na2-binding site. Our findings highlight the structural role of Na + at the Na2 sites in driving conformational changes in the protein required for sugar stabilization and the subsequent closing of the outer gate.
Zheng et al. (Sun,) studied this question.