Cryo-EM structure of the human glucose transporter GLUT7.

ABSTRACT

GLUT7 is a Class II glucose transporter predominantly expressed at the apical membrane of enterocytes in the small intestine. Here, we report the cryo-EM structure of nanodisc-reconstituted human GLUT7 in the apo state at 3.3 Å resolution. Our atomic model reveals a typical major facilitator superfamily fold, with the substrate-binding site open to the extracellular side of the membrane. Despite the nearly identical conformation to its closest family member, rat GLUT5, our structure unveils distinct features of the substrate-binding cavity that may influence substrate specificity and binding mode. A homology model of the inward-open human GLUT7 indicates that similar to other members of the GLUT family, it may undergo a global rocker-switch-like reorientation of the transmembrane bundles to facilitate substrate translocation across the membrane. Our work enhances the current structural understanding of the GLUT family, and lays a foundation for rational design of regulators of GLUTs and other sugar transporters.