Secondary active transporter proteins move target molecules across a cellular membrane against their electrochemical gradient by coupling that process to a pre-existing gradient of another molecule or ion. In a majority of cases, the energy source is a proton or sodium ion. Potassium ion gradients, when involved, are typically directed in the opposite direction from that of sodium. The specificity of these energy sources raises the question of how transporter proteins accomplish cation selectivity such that none of the other gradients are unintentionally dissipated. In this talk, I will offer a holistic explanation for cation coupling and selectivity by a neurotransmitter transporter in the SLC6 family. These insights emerge from judiciously designed molecular dynamics simulations guided and informed by biochemical and electrophysiological measurements by our collaborators.
Lucy R. Forrest (Sun,) studied this question.