ArticleThe Journal of biological chemistry2013
Molecular basis of cannabinoid CB1 receptor coupling to the G protein heterotrimer Gαiβγ: identification of key CB1 contacts with the C-terminal helix α5 of Gαi.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Article
- Side-Chain Homologs of ΔMolecular neurobiology · 2026Article
- Differential Behavior of Conformational Dynamics in Active and Inactive States of Cannabinoid Receptor 1.The journal of physical chemistry. B · 2024Article
- A Structure Independent Molecular Fragment Interfuse Model for Mesoscale Dissipative Particle Dynamics Simulation of Peptides.ACS omega · 2024Article
- Prediction of essential binding domains for the endocannabinoid N-arachidonoylethanolamine (AEA) in the brain cannabinoid CB1 receptor.PloS one · 2021Article
- Structural Insights into CB1 Receptor Biased Signaling.International journal of molecular sciences · 2019Review
- Recent advances in computational studies of GPCR-G protein interactions.Advances in protein chemistry and structural biology · 2019Review
- The F238L Point Mutation in the Cannabinoid Type 1 Receptor Enhances Basal Endocytosis via Lipid Rafts.Frontiers in molecular neuroscience · 2018Article
- C-terminus of OX2R significantly affects downstream signaling pathways.Molecular medicine reports · 2017Article
- Cortical adrenoceptor expression, function and adaptation under conditions of cannabinoid receptor deletion.Experimental neurology · 2017Article
- Recent Progress in Understanding the Conformational Mechanism of Heterotrimeric G Protein Activation.Biomolecules & therapeutics · 2017Review
- Functional Role of the C-Terminal Amphipathic Helix 8 of Olfactory Receptors and Other G Protein-Coupled Receptors.International journal of molecular sciences · 2016Review
- A G-protein Subunit-α11 Loss-of-Function Mutation, Thr54Met, Causes Familial Hypocalciuric Hypercalcemia Type 2 (FHH2).Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2016Article
- Computational analysis of the CB1 carboxyl-terminus in the receptor-G protein complex.Proteins · 2016Article
- Ethanol effects on glycinergic transmission: From molecular pharmacology to behavior responses.Pharmacological research · 2015Review
- Minireview: From the bench, toward the clinic: therapeutic opportunities for cannabinoid receptor modulation.Molecular endocrinology (Baltimore, Md.) · 2015Review
- Evidence for α-helices in the large intracellular domain mediating modulation of the α1-glycine receptor by ethanol and Gβγ.The Journal of pharmacology and experimental therapeutics · 2015Article
- Role of Structural Dynamics at the Receptor G Protein Interface for Signal Transduction.PloS one · 2015Article
- Ligand-specific endocytic dwell times control functional selectivity of the cannabinoid receptor 1.Nature communications · 2014Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The cannabinoid (CB1) receptor is a member of the rhodopsin-like G protein-coupled receptor superfamily. The human CB1 receptor, which is among the most expressed receptors in the brain, has been implicated in several disease states, including drug addiction, anxiety, depression, obesity, and chronic pain. Different classes of CB1 agonists evoke signaling pathways through the activation of specific subtypes of G proteins. The molecular basis of CB1 receptor coupling to its cognate G protein is unknown. As a first step toward understanding CB1 receptor-mediated G protein signaling, we have constructed a ternary complex structural model of the CB1 receptor and Gi heterotrimer (CB1-Gi), guided by the x-ray structure of β2-adrenergic receptor (β2AR) in complex with Gs (β2AR-Gs), through 824-ns duration molecular dynamics simulations in a fully hydrated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayer environment. We identified a group of residues at the juxtamembrane regions of the intracellular loops 2 and 3 (IC2 and IC3) of the CB1 receptor, including Ile-218(3.54), Tyr-224(IC2), Asp-338(6.30), Arg-340(6.32), Leu-341(6.33), and Thr-344(6.36), as potential key contacts with the extreme C-terminal helix α5 of Gαi. Ala mutations of these residues at the receptor-Gi interface resulted in little G protein coupling activity, consistent with the present model of the CB1-Gi complex, which suggests tight interactions between CB1 and the extreme C-terminal helix α5 of Gαi. The model also suggests that unique conformational changes in the extreme C-terminal helix α5 of Gα play a crucial role in the receptor-mediated G protein activation.
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