Cannabinoid Receptor Type 2 - Structure

Structure

The CB₂ receptor is encoded by the CNR2 gene. Approximately 360 amino acids comprise the human CB₂ receptor, making it somewhat shorter than the 473-amino-acid-long CB₁ receptor.

As is commonly seen in G protein-coupled receptors, the CB₂ receptor has seven transmembrane spanning domains, a glycosylated N-terminus, and an intracellular C-terminus. The C-terminus of CB₂ receptors appears to play a critical role in the regulation of ligand-induced receptor desensitization and downregulation following repeated agonist application, perhaps causing the receptor to become less responsive to particular ligands.

The human CB₁ and the CB₂ receptors possess approximately 44% amino acid similarity. When only the transmembrane regions of the receptors are considered, however, the amino acid similarity between the two receptor subtypes is approximately 68%. The amino acid sequence of the CB₂ receptor is less highly conserved across human and rodent species as compared to the amino acid sequence of the CB₁ receptor. Based on computer modeling, ligand interactions with CB₂ receptor residues S3.31 and F5.46 appears to determine differences between CB₁ and CB₂ receptor selectivity. In CB₂ receptors, lipophilic groups interact with the F5.46 residue, allowing them to form a hydrogen bond with the S3.31 residue. These interactions induce a conformational change in the receptor structure, which triggers the activation of various intracellular signaling pathways. Further research is needed to determine the exact molecular mechanisms of signaling pathway activation.