A biophysical glance at the outer surface of the membrane transporter SGLT1

► Biophysical approaches can be used to strengthen functional and structural information of SGLT1. ► Direct evidence of the initial D-glucose-binding site requiring the presence of sodium. ► Large extracellular loops of SGLT1 act as the vestibule for substrate binding. ► Loop 13 of SGLT1 localizes extracellularly. Loop 13 is involved in the binding of phlorizin to SGLT1.