Type-1 Cannabinoid Receptor Promiscuous Coupling: Computational Insights into Receptor-G Protein Interaction Dynamics.

ABSTRACT: Cannabinoid receptor (CB1), a G protein coupled receptor (GPCR), is a known pharmacological target in several diseases and modulates key physiological processes through Gi protein-mediated signaling. However, recent evidence suggests that CB1 can also activate other G proteins, including the stimulatory Gs protein, a phenomenon with unclear structural determinants. Here, we use a computational approach to elucidate the structural basis of the CB1-Gs interaction. Protein-protein docking and extensive molecular dynamics simulations yield a model for the CB1-Gs complex that agrees well with both existing experimental data and available GPCR-Gs structures, supporting its validity. This work provides new insights into the structural basis of CB1's ability to couple with different G-proteins. Th

SUBMITTER: Berghella A 

PROVIDER: S-EPMC12732796 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature