ArticleScience advances2021
Illumination of serotonin transporter mechanism and role of the allosteric site.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed.
- Article
- Structural basis of the transport mechanism of hBGT1.Cell discovery · 2026Article
- Structural and functional basis of antinociceptive action of χ-conotoxin AoIA at the noradrenaline transporter.Nature structural & molecular biology · 2026Article
- Neurotropic potential and docking investigations of newly synthesized triazolopyridine and triazolothienopyridine derivatives.RSC advances · 2026Article
- Cytosolic KJournal of chemical theory and computation · 2026Article
- Beyond neurotransmission: the roles of serotonylation in physiological and pathological processes.Cellular & molecular biology letters · 2026Review
- The Role of Cholesterol at the CHOL2 Site and the Dimeric Interface in the Regulation of Serotonin Transporter Function and Dimerization.Biomolecules · 2026Article
- Structural mechanism of substrate binding and inhibition of human taurine transporter.Nature communications · 2026Article
- Probiotic-Driven Metabolic Transformation in Dark Tea: Enhanced Bioactives and Gut Microbiota Modulation Underlie Its Alleviation Effect Against Constipation.Foods (Basel, Switzerland) · 2026Article
- Inhibitors of Sodium-Dependent Serotonin Transporter Protein (SERT) as Potential New Nematicides.Chemistry & biodiversity · 2026Article
- Partial Serotonin Transporter Deficiency Modulates Plasma Metabolome, Arginine-Nitric Oxide Pathway and Emotional Behavior in Mice Exposed to Western Diet.Metabolites · 2026Article
- Cell membrane cholesterol affects serotonin transporter efflux due to altered transporter oligomerization.Molecular psychiatry · 2026Article
- Structural basis for selective inhibition of human GABA transporter GAT3.Nature communications · 2026Article
- Deciphering Ibogaine's Matrix Pharmacology: Multiple Transporter Modulation at Serotonin Synapses.Journal of the American Chemical Society · 2026Article
- The Nanodisc System for Investigating Protein-Lipid Interactions.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Next-Generation MDMA Analogue SDMA: Pharmacological and Metabolic Insights.ACS chemical neuroscience · 2025Article
- Prolintane analogs as hybrid monoamine transporter ligands: Structural determinants and species differences.The Journal of biological chemistry · 2025Article
- Inhibition of SERT and NMDAR synergistically confers rapid antidepressant effects of ketamine.National science review · 2025Article
- Structural pharmacology of SV2A reveals an allosteric modulation mechanism in the major facilitator superfamily.Nature communications · 2025Article
- Structural basis of vilazodone dual binding mode to the serotonin transporter.Nature communications · 2025Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
The serotonin transporter (SERT) terminates serotonin signaling by using sodium and chloride gradients to drive reuptake of serotonin into presynaptic neurons and is the target of widely used medications to treat neuropsychiatric disorders. Despite decades of study, the molecular mechanism of serotonin transport, the coupling to ion gradients, and the role of the allosteric site have remained elusive. Here, we present cryo–electron microscopy structures of SERT in serotonin-bound and serotonin-free states, in the presence of sodium or potassium, resolving all fundamental states of the transport cycle. From the SERT-serotonin complex, we localize the substrate-bound allosteric site, formed by an aromatic pocket positioned in the scaffold domain in the extracellular vestibule, connected to the central site via a short tunnel. Together with elucidation of multiple apo state conformations, we provide previously unseen structural understanding of allosteric modulation, demonstrating how SERT binds serotonin from synaptic volumes and promotes unbinding into the presynaptic neurons.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.