Crystal structure of a glucose/H+ symporter and its mechanism of action

Abstract

Glucose transporters are required to bring glucose into cells, where it is an essential energy source and precursor in protein and lipid synthesis. These transporters are involved in important common diseases such as cancer and diabetes. Here, we report the crystal structure of the Staphylococcus epidermidis glucose/H+ symporter in an inward-facing conformation at 3.2-A resolution. The Staphylococcus epidermidis glucose/H+ symporter is homologous to human glucose transporters, is very specific and has high avidity for glucose, and is inhibited by the human glucose transport inhibitors cytochalasin B, phloretin, and forskolin. On the basis of the crystal structure in conjunction with mutagenesis and functional studies, we propose a mechanism for glucose/H+ symport and discuss the symport mechanism versus facilitated diffusion.