ArticleNature2013
X-ray structure of dopamine transporter elucidates antidepressant mechanism.
Article in Nature, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 383 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
383 citing papers in PubMed, 1 synthesis or guideline pooled it, 630 citations in OpenAlex.
- Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review.Psychopharmacology · 2022Pooled it
- Disruption of dopamine transmission by cholesterol depletion is associated with alterations in protein lipid raft partitioning and actin dynamics.Neuropharmacology · 2026Article
- Structural basis of the transport mechanism of hBGT1.Cell discovery · 2026Article
- Reversible, Chemically Gated FRET via Ligand-Activated Acceptors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Emerging roles of SLC6A14 in digestive system diseases: from amino acid transport to therapeutic targeting.Molecular biology reports · 2026Review
- pH-dependent activation of the NaNature communications · 2026Article
- Synthesis, Antidepressant-like and Anxiolytic-like Effects of Novel Thiadiazole Derivatives: Behavioral Assessment and Mechanistic Investigation.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Structural basis for the transport mechanism and cholesterol modulation of the human proline transporter.Nature communications · 2026Article
- The Role of Cholesterol at the CHOL2 Site and the Dimeric Interface in the Regulation of Serotonin Transporter Function and Dimerization.Biomolecules · 2026Article
- Structural bases of signal generation and transduction by the SPS amino acid sensor of Saccharomyces cerevisiae.G3 (Bethesda, Md.) · 2026Article
- A reversible allosteric inhibitor of GlyT2 for neuropathic pain without on-target side effects.Nature communications · 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
- Synaptic plasticity in affective comorbidities of neuropathic pain: a bibliometric analysis based on WoSCC and PubMed (2003-2025).Frontiers in neurology · 2026Article
- A reversible allosteric inhibitor of GlyT2 alleviates neuropathic pain without on-target side effects.bioRxiv : the preprint server for biology · 2025Article
- Transient Suppression of Dopamine Transporter Palmitoylation by Methamphetamine: Implications for Transport Regulation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Mutational effects of the asparagine198 and glutamate223 residues on the human norepinephrine transporter on basal and HIV-1 Tat protein-induced inhibition of dopamine transport.European journal of pharmacology · 2025Article
- 1-Nitro-2-Phenylethane as a Multitarget Candidate for Cognitive and Psychiatric Disorders: Insights from In Silico and Behavioral Approaches.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Dual sigma receptor/dopamine transporter inhibition and the union of pharmacology and experimental psychology.The Journal of pharmacology and experimental therapeutics · 2025Review
- Repurposing drugs for the human dopamine transporter through WHALES descriptors-based virtual screening and bioactivity evaluation.Journal of pharmaceutical analysis · 2025Article
323 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Antidepressants targeting Na(+)/Cl(-)-coupled neurotransmitter uptake define a key therapeutic strategy to treat clinical depression and neuropathic pain. However, identifying the molecular interactions that underlie the pharmacological activity of these transport inhibitors, and thus the mechanism by which the inhibitors lead to increased synaptic neurotransmitter levels, has proven elusive. Here we present the crystal structure of the Drosophila melanogaster dopamine transporter at 3.0 Å resolution bound to the tricyclic antidepressant nortriptyline. The transporter is locked in an outward-open conformation with nortriptyline wedged between transmembrane helices 1, 3, 6 and 8, blocking the transporter from binding substrate and from isomerizing to an inward-facing conformation. Although the overall structure of the dopamine transporter is similar to that of its prokaryotic relative LeuT, there are multiple distinctions, including a kink in transmembrane helix 12 halfway across the membrane bilayer, a latch-like carboxy-terminal helix that caps the cytoplasmic gate, and a cholesterol molecule wedged within a groove formed by transmembrane helices 1a, 5 and 7. Taken together, the dopamine transporter structure reveals the molecular basis for antidepressant action on sodium-coupled neurotransmitter symporters and elucidates critical elements of eukaryotic transporter structure and modulation by lipids, thus expanding our understanding of the mechanism and regulation of neurotransmitter uptake at chemical synapses.
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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.