title: A Candidate Ion-Retaining State in the Inward-Facing Conformation of Sodium/Galactose Symporter: Clues from Atomistic Simulations.
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). A recent study, based on molecular dynamics simulations, showed that the sodium ion spontaneously leaves its initial position diffusing outside vSGLT, toward the intracellular space. This suggested that the crystal structure corresponds to an ion-releasing state of the transporter. Here, using metadynamics, we identified a more stable Na(+) binding site corresponding to a putative ion-retaining state of the transporter. In addition, our simulations, consistently with mutagenesis studies, highlight the importance of D189 that, without being one of the Na(+)-coordinating residues, regulates its binding/release.
authors.affiliation: SISSA , Via Bonomea 265, 34165 Trieste, Italy.
authors.forename: Ina
authors.initials: I
authors.lastname: Bisha
authors.affiliation: SISSA , Via Bonomea 265, 34165 Trieste, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Laio
authors.affiliation: CNR-IOM-Democritos National Simulation Center c/o SISSA , via Bonomea 265, 34165 Trieste, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Magistrato
authors.affiliation: University of Verona , Ca' Vignal 1, Strada Le Grazie 15, 37134 Verona, Italy.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Giorgetti
authors.affiliation: CNR-IOM-Democritos National Simulation Center c/o SISSA , via Bonomea 265, 34165 Trieste, Italy.
authors.forename: Jacopo
authors.initials: J
authors.lastname: Sgrignani