Substrate-modulated gating dynamics in a Na+-coupled neurotransmitter transporter homologue

Neurotransmitters are removed from the synapse by neurotransmitter/Na+ symporters (NSSs) in a reuptake process driven by the Na+ gradient. Zhao et al. examined the coupling of substrate binding to structural transitions in the prokaryotic NSS homologue LeuT. Using single-molecule fluorescence resonance energy transfer, functional experiments and computational studies, they find that LeuT facilitates intracellular gate opening and substrate release at the intracellular face of the protein.