ArticleNature chemical biology2022
Molecular mechanism of allosteric modulation for the cannabinoid receptor CB1.
Article in Nature chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
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Who cites it
54 citing papers in PubMed, 95 citations in OpenAlex.
- Molecular mechanism of allosteric modulation of opioid receptors.Signal transduction and targeted therapy · 2026Article
- Dynamic mechanism for subtype selectivity of endocannabinoids.The Journal of biological chemistry · 2026Article
- Structural basis for positive allosteric regulation of CB2 receptor.Nature communications · 2026Article
- Structural and dynamic studies uncover a distinct allosteric modulatory site at the µ-opioid receptor.Nature communications · 2026Article
- Structure-based design of an opioid receptor modulator for enhanced morphine analgesia.Science advances · 2026Article
- Targeting cannabinoid receptor 1 for multiple sclerosis: molecular docking and dynamic insights of berberine and curcumin as potential therapeutic agents.American journal of clinical and experimental immunology · 2026Article
- Structural Perspectives on Biased Allostery of GPCR Signaling.Handbook of experimental pharmacology · 2026Review
- From CASP13 to the Nobel Prize: DeepMind's AlphaFold Journey in Revolutionizing Protein Structure Prediction and Beyond.Current protein & peptide science · 2026Review
- Type-1 Cannabinoid Receptor Promiscuous Coupling: Computational Insights into Receptor-G Protein Interaction Dynamics.International journal of molecular sciences · 2025Article
- Elucidating biased signaling in class A GPCRs.Trends in pharmacological sciences · 2025Review
- Structure-guided allosteric modulation of the delta opioid receptor.bioRxiv : the preprint server for biology · 2025Article
- Allosteric Modulation of Cannabinoid Type 1 Receptor by ZCZ011: Integration of In Vitro Pharmacology and Molecular Dynamics Simulation.ACS bio & med chem Au · 2025Article
- Benzo[International journal of molecular sciences · 2025Article
- Effects of Membrane Cholesterol on the Structure and Function of Selected Class A GPCRs─Challenges and Future Perspectives.Biochemistry · 2025Review
- The Endocannabinoid System in the Development and Treatment of Obesity: Searching for New Ideas.International journal of molecular sciences · 2025Review
- Efficient Characterization of GPCRs Allosteric Modulation: Application to the Rational Design of De Novo S1PR1 Allosteric Modulators.Journal of chemical information and modeling · 2025Article
- Advances in cannabinoid receptors pharmacology: from receptor structural insights to ligand discovery.Acta pharmacologica Sinica · 2025Review
- Development of Squaramides as Allosteric Modulators of the CBJournal of medicinal chemistry · 2025Article
- Noncovalent Interaction-Based Probe Design for PET-Facilitated Fluorescence Sensing of Synthetic Cannabinoids.ACS omega · 2025Article
- Article
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Given the promising clinical value of allosteric modulators of G protein-coupled-receptors (GPCRs), mechanistic understanding of how these modulators alter GPCR function is of significance. Here, we report the crystallographic and cryo-electron microscopy structures of the cannabinoid receptor CB1 bound to the positive allosteric modulator (PAM) ZCZ011. These structures show that ZCZ011 binds to an extrahelical site in the transmembrane 2 (TM2)-TM3-TM4 surface. Through (un)biased molecular dynamics simulations and mutagenesis experiments, we show that TM2 rearrangement is critical for the propagation of allosteric signals. ZCZ011 exerts a PAM effect by promoting TM2 rearrangement in favor of receptor activation and increasing the population of receptors that adopt an active conformation. In contrast, ORG27569, a negative allosteric modulator (NAM) of CB1, also binds to the TM2-TM3-TM4 surface and exerts a NAM effect by impeding the TM2 rearrangement. Our findings fill a gap in the understanding of CB1 allosteric regulation and could guide the rational design of CB1 allosteric modulators.
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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 Socratic graph.