Crystal structure of SGLT reveals mechanism of Na+/sugar cotransport

Abstract

Membrane proteins that convert energy stored in electrochemical sodium gradients to drive nutrients into cells constitute a major class of proteins widely distributed throughout all kingdoms of life. We recently reported the crystal structure of a representative member of the SSS family, the Vibrio parahaemolyticus sodium/galactose symporter (vSGLT). This transporter is homologous to human members of the SSS family that are important in health and disease. The ~3.0′ structure shows 14 transmembrane helices with a core structure composed of inverted repeats of 5 TM helices (TM2‐TM6 and TM7‐TM11). In the center of the core resides a bound galactose that is occluded, by hydrophobic residues, from a large aqueous cavity open to the intracellular milieu, representing the inward‐facing conformation. The architecture of the core is similar to both the leucine transporter (LeuT) and the more recently reported Benzyl‐hydantoin transporter (Mhp1) from different gene families. Modeling the outward‐facing conformation based on LeuT amd Mhp1 structures, in conjunction with biophysical data, provides insight into structural rearrangements for active transport.