ArticleNature communications2024
Structural basis for the transmembrane signaling and antidepressant-induced activation of the receptor tyrosine kinase TrkB.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The trial behind it
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
12 citing papers in PubMed.
- Molecular neurobiological insights on integrative role of Trk neurotrophic receptors and their small-molecule agonists in neurodegenerative conditions.Experimental brain research · 2026Review
- Discovery of a sulfotyrosine-motif in the human TrkB extracellular domain required for agonist activation.bioRxiv : the preprint server for biology · 2026Article
- TrkB/mGluR5 cross-talk underlies a synaptic metaplasticity mechanism of ketamine.Science advances · 2026Article
- Molecular determinants of signal transduction in tropomyosin receptor kinases.FEBS open bio · 2026Review
- OrthogonalApplied and environmental microbiology · 2025Article
- Transmembrane domain interactions underlie NSG1 regulation of sortilin ectodomain shedding.The Journal of biological chemistry · 2025Article
- Review
- The therapeutic potential of psilocybin beyond psychedelia through shared mechanisms with ketamine.Molecular psychiatry · 2025Review
- Simulation of Neurotrophin Receptor Transmembrane Helix Interactions Reveals Active States and Distinct Signaling Mechanisms.JACS Au · 2025Article
- Neurotrophic factors as double-edged swords in osteosarcoma: drivers of tumour growth and immune remodelling.Frontiers in immunology · 2025Review
- Beyond the 5-HTThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Review
- Facade-Based Bicelles as a New Tool for Production of Active Membrane Proteins in a Cell-Free System.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Neurotrophin receptors of the Trk family are involved in the regulation of brain development and neuroplasticity, and therefore can serve as targets for anti-cancer and stroke-recovery drugs, antidepressants, and many others. The structures of Trk protein domains in various states upon activation need to be elucidated to allow rational drug design. However, little is known about the conformations of the transmembrane and juxtamembrane domains of Trk receptors. In the present study, we employ NMR spectroscopy to solve the structure of the TrkB dimeric transmembrane domain in the lipid environment. We verify the structure using mutagenesis and confirm that the conformation corresponds to the active state of the receptor. Subsequent study of TrkB interaction with the antidepressant drug fluoxetine, and the antipsychotic drug chlorpromazine, provides a clear self-consistent model, describing the mechanism by which fluoxetine activates the receptor by binding to its transmembrane domain.
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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.