ReviewCurrent medicinal chemistry2012
Action of molecular switches in GPCRs--theoretical and experimental studies.
Review in Current medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 210 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
210 citing papers in PubMed, 471 citations in OpenAlex.
- Molecular Dynamics and Electron Density Topology Reveal Ligand-Specific Interaction Patterns at the Dopamine DInternational journal of molecular sciences · 2026Article
- Structural determinants of ligand response specificity in the mast cell activating GPCR, MRGPRX2.The Journal of biological chemistry · 2026Article
- Elucidating the Structure and Activation Mechanisms of GPCRs Using Modern Computational and AI Tools.Cell biochemistry and biophysics · 2026Review
- Computational Insights into the Activation Mechanism of CXCR4: Implications for the Design of Small Molecule Agonists.Journal of the American Chemical Society · 2026Article
- A structural overview of G-protein-coupled receptors in neurological disorders.Acta pharmacologica Sinica · 2026Review
- Binding pose depth modulates photoswitchable ligands' efficacy at the 5-HTCommunications chemistry · 2026Article
- Novel GαGTP Sensors Reveal Endogenous and Subcellular G Protein Signaling Dynamics.bioRxiv : the preprint server for biology · 2026Article
- Atypical GPCR Activation Resolved by Nanobody Engineering.bioRxiv : the preprint server for biology · 2026Article
- Adhesion G-Protein Coupled Receptors in Neurological and Psychiatric Disorders.Journal of psychiatry and brain science · 2025Article
- Computational modelling reveals novel insights into GnRH receptor activation and binding dynamics.Scientific reports · 2025Article
- GPR25 promotes the formation of lung and liver tissue-resident memory CD8 T cells.Science immunology · 2025Article
- Biased signalingActa pharmaceutica Sinica. B · 2025Review
- Non-canonical GScientific reports · 2025Article
- Identification of a Lipid-Exposed Extrahelical Binding Site for Positive Allosteric Modulators of the Dopamine DACS chemical neuroscience · 2025Article
- CXC Chemokine Ligand 12 Facilitates Gi Protein Binding to CXC Chemokine Receptor 4 by Stabilizing Packing of the Proline-Isoleucine-Phenylalanine Motif: Insights from Automated Path Searching.Journal of the American Chemical Society · 2025Article
- Intracellular Pocket Conformations Determine Signaling Efficacy through the μ Opioid Receptor.Journal of chemical information and modeling · 2025Article
- G protein-coupled receptors in prostate cancer: research progress and therapeutic targets.Frontiers in cell and developmental biology · 2025Review
- Intracellular pocket conformations determine signaling efficacy through thebioRxiv : the preprint server for biology · 2024Article
- Molecular basis for chemokine recognition and activation of XCR1.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Molecular Dynamics (MD) Simulations Provide Insights into the Activation Mechanisms of 5-HTMolecules (Basel, Switzerland) · 2024Article
150 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
G protein coupled receptors (GPCRs), also called 7TM receptors, form a huge superfamily of membrane proteins that, upon activation by extracellular agonists, pass the signal to the cell interior. Ligands can bind either to extracellular N-terminus and loops (e.g. glutamate receptors) or to the binding site within transmembrane helices (Rhodopsin-like family). They are all activated by agonists although a spontaneous auto-activation of an empty receptor can also be observed. Biochemical and crystallographic methods together with molecular dynamics simulations and other theoretical techniques provided models of the receptor activation based on the action of so-called "molecular switches" buried in the receptor structure. They are changed by agonists but also by inverse agonists evoking an ensemble of activation states leading toward different activation pathways. Switches discovered so far include the ionic lock switch, the 3-7 lock switch, the tyrosine toggle switch linked with the nPxxy motif in TM7, and the transmission switch. The latter one was proposed instead of the tryptophan rotamer toggle switch because no change of the rotamer was observed in structures of activated receptors. The global toggle switch suggested earlier consisting of a vertical rigid motion of TM6, seems also to be implausible based on the recent crystal structures of GPCRs with agonists. Theoretical and experimental methods (crystallography, NMR, specific spectroscopic methods like FRET/BRET but also single-molecule-force-spectroscopy) are currently used to study the effect of ligands on the receptor structure, location of stable structural segments/domains of GPCRs, and to answer the still open question on how ligands are binding: either via ensemble of conformational receptor states or rather via induced fit mechanisms. On the other hand the structural investigations of homoand heterodimers and higher oligomers revealed the mechanism of allosteric signal transmission and receptor activation that could lead to design highly effective and selective allosteric or ago-allosteric drugs.
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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.