Conformational dynamics of the human serotonin transporter during substrate and drug binding.
Nature communications April 11, 2019 Ingvar R Möller, Marika Slivacka, Anne Kathrine Nielsen et al. 92 citations
The serotonin transporter (SERT) clears serotonin from the synapse, making it a key target for antidepressants and other drugs. Using hydrogen-deuterium exchange mass spectrometry, the authors mapped changes in SERT's shape and flexibility when it binds sodium and potassium ions, the neurotransmitter serotonin, and the drugs S-citalopram, cocaine, and ibogaine. Binding altered dynamics in specific structural regions: TM1, EL3, EL4, and TM12 for ions, and TM1, EL3, and EL4 for the other ligands. These results offer a direct view of how SERT responds to both natural substrates and pharmaceutical compounds, deepening understanding of its structure and function.