jacopo sgrignani

Abstract: The recent Vibrio parahaemolyticus sodium/galactose (vSGLT) symporter crystal structure captures the protein in an inward-facing substrate-bound conformation, with the sodium ion placed, by structural alignment, in a site equivalent to the Na2 site of the leucine transporter (LeuT). Recent studies, based on molecular dynamics simulations, showed that the sodium ion spontaneously leaves its starting position diffusing outside vSGLT, towards the intracellular space. This led to the conclusion that the crystal structure corresponds to an ion-releasing state of the transporter. Here, using metadynamics, we identified a Na+ binding site corresponding to an ion-retaining state of the transporter. In addition, our simulations, consistently with mutagenesis studies, highlight the important role of D189 that, without being one of the ion- coordinating residues, regulates the Na+ binding/release.