ArticleACS chemical neuroscience2020
Membrane-Dependent Binding and Entry Mechanism of Dopamine into Its Receptor.
Article in ACS chemical neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Uncovering the Lipid Interface in Neurotransmission: Single Molecule Measurements of Neurotransmitters Interacting with Membranes Reveal Species Dependent Membrane Binding.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Automated parametrization of small molecules within the Martini 3 coarse-grained model guided by experimental log P values.Scientific reports · 2025Article
- SPLICEIT Fluorescent Sensor for Integrating Dopamine Release with Cellular Resolution.Angewandte Chemie (International ed. in English) · 2025Article
- Neurotoxicology of dopamine: Victim or assailant?Neurotoxicology · 2024Review
- Ligand entry pathways control the chemical space recognized by GPR183.Chemical science · 2023Article
- How Neuromembrane Lipids Modulate Membrane Proteins: Insights from G-Protein-Coupled Receptors (GPCRs) and Receptor Tyrosine Kinases (RTKs).Cold Spring Harbor perspectives in biology · 2023Review
- Controlled Delivery of Celecoxib-β-Cyclodextrin Complexes from the Nanostructured Titanium Dioxide Layers.Pharmaceutics · 2023Article
- Permeation of a Homologous Series of NBD-Labeled Fatty Amines through Lipid Bilayers: A Molecular Dynamics Study.Membranes · 2023Article
- Impact of membrane lipid polyunsaturation on dopamine D2 receptor ligand binding and signaling.Molecular psychiatry · 2023Article
- Ligand's Partition to the Lipid Bilayer Should Be Accounted for When Estimating Their Affinity to Proteins.Molecules (Basel, Switzerland) · 2023Article
- Location of dopamine in lipid bilayers and its relevance to neuromodulator function.Biophysical journal · 2023Article
- Membrane Lipids Are an Integral Part of Transmembrane Allosteric Sites in GPCRs: A Case Study of Cannabinoid CB1 Receptor Bound to a Negative Allosteric Modulator, ORG27569, and Analogs.Journal of medicinal chemistry · 2022Article
- Analysis of the Equilibrium Distribution of Ligands in Heterogeneous Media-Approaches and Pitfalls.International journal of molecular sciences · 2022Review
- Examining the Effect of Charged Lipids on Mitochondrial Outer Membrane Dynamics Using Atomistic Simulations.Biomolecules · 2022Article
- Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Mechanistic Understanding From Molecular Dynamics Simulation in Pharmaceutical Research 1: Drug Delivery.Frontiers in molecular biosciences · 2020Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synaptic neurotransmission has recently been proposed to function via either a membrane-independent or a membrane-dependent mechanism, depending on the neurotransmitter type. In the membrane-dependent mechanism, amphipathic neurotransmitters first partition to the lipid headgroup region and then diffuse along the membrane plane to their membrane-buried receptors. However, to date, this mechanism has not been demonstrated for any neurotransmitter-receptor complex. Here, we combined isothermal calorimetry measurements with a diverse set of molecular dynamics simulation methods to investigate the partitioning of an amphipathic neurotransmitter (dopamine) and the mechanism of its entry into the ligand-binding site. Our results show that the binding of dopamine to its receptor is consistent with the membrane-dependent binding and entry mechanism. Both experimental and simulation results showed that dopamine favors binding to lipid membranes especially in the headgroup region. Moreover, our simulations revealed a ligand-entry pathway from the membrane to the binding site. This pathway passes through a lateral gate between transmembrane alpha-helices 5 and 6 on the membrane-facing side of the protein. All in all, our results demonstrate that dopamine binds to its receptor by a membrane-dependent mechanism, and this is complemented by the more traditional binding mechanism directly through the aqueous phase. The results suggest that the membrane-dependent mechanism is common in other synaptic receptors, too.
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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.