ArticleThe Journal of biological chemistry2014
Structural basis of G protein-coupled receptor-Gi protein interaction: formation of the cannabinoid CB2 receptor-Gi protein complex.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Structural basis for ligand promiscuity and high signaling activity of Kaposi's Sarcoma-associated Herpesvirus-encoded GPCR.Nature communications · 2025Article
- Molecular mechanism of muscarinic acetylcholine receptor M3 interaction with Gq.Communications biology · 2024Article
- GαPharmacological reports : PR · 2023Article
- Article
- State-dependent Lipid Interactions with the A2a Receptor Revealed by MD Simulations Using In Vivo-Mimetic Membranes.Structure (London, England : 1993) · 2019Article
- Article
- Recent advances in computational studies of GPCR-G protein interactions.Advances in protein chemistry and structural biology · 2019Review
- G protein-coupled receptor kinases: Past, present and future.Cellular signalling · 2018Article
- Allosteric modulation model of the mu opioid receptor by herkinorin, a potent not alkaloidal agonist.Journal of computer-aided molecular design · 2017Article
- Methods for the Development of In Silico GPCR Models.Methods in enzymology · 2017Article
- Recent Progress in Understanding the Conformational Mechanism of Heterotrimeric G Protein Activation.Biomolecules & therapeutics · 2017Review
- Mechanistic insights into GPCR-G protein interactions.Current opinion in structural biology · 2016Review
- Chromenopyrazole, a Versatile Cannabinoid Scaffold with in Vivo Activity in a Model of Multiple Sclerosis.Journal of medicinal chemistry · 2016Article
- Multi-Functional Diarylurea Small Molecule Inhibitors of TRPV1 with Therapeutic Potential for Neuroinflammation.The AAPS journal · 2016Article
- Difference and Influence of Inactive and Active States of Cannabinoid Receptor Subtype CB2: From Conformation to Drug Discovery.Journal of chemical information and modeling · 2016Article
- Computational Simulation of the Activation Cycle of Gα Subunit in the G Protein Cycle Using an Elastic Network Model.PloS one · 2016Article
- Cannabinoid CB2 Receptor Mediates Nicotine-Induced Anti-Inflammation in N9 Microglial Cells Exposed to β Amyloid via Protein Kinase C.Mediators of inflammation · 2016Article
- Article
- Minireview: From the bench, toward the clinic: therapeutic opportunities for cannabinoid receptor modulation.Molecular endocrinology (Baltimore, Md.) · 2015Review
- Role of Structural Dynamics at the Receptor G Protein Interface for Signal Transduction.PloS one · 2015Article
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10 authors.
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Abstract
In this study, we applied a comprehensive G protein-coupled receptor-Gαi protein chemical cross-linking strategy to map the cannabinoid receptor subtype 2 (CB2)-Gαi interface and then used molecular dynamics simulations to explore the dynamics of complex formation. Three cross-link sites were identified using LC-MS/MS and electrospray ionization-MS/MS as follows: 1) a sulfhydryl cross-link between C3.53(134) in TMH3 and the Gαi C-terminal i-3 residue Cys-351; 2) a lysine cross-link between K6.35(245) in TMH6 and the Gαi C-terminal i-5 residue, Lys-349; and 3) a lysine cross-link between K5.64(215) in TMH5 and the Gαi α4β6 loop residue, Lys-317. To investigate the dynamics and nature of the conformational changes involved in CB2·Gi complex formation, we carried out microsecond-time scale molecular dynamics simulations of the CB2 R*·Gαi1β1γ2 complex embedded in a 1-palmitoyl-2-oleoyl-phosphatidylcholine bilayer, using cross-linking information as validation. Our results show that although molecular dynamics simulations started with the G protein orientation in the β2-AR*·Gαsβ1γ2 complex crystal structure, the Gαi1β1γ2 protein reoriented itself within 300 ns. Two major changes occurred as follows. 1) The Gαi1 α5 helix tilt changed due to the outward movement of TMH5 in CB2 R*. 2) A 25° clockwise rotation of Gαi1β1γ2 underneath CB2 R* occurred, with rotation ceasing when Pro-139 (IC-2 loop) anchors in a hydrophobic pocket on Gαi1 (Val-34, Leu-194, Phe-196, Phe-336, Thr-340, Ile-343, and Ile-344). In this complex, all three experimentally identified cross-links can occur. These findings should be relevant for other class A G protein-coupled receptors that couple to Gi proteins.
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