The cannabinoid receptor CB1 belongs to an important family of receptors with 7 transmembrane helixs also called, G-protein coupled receptors (GPCRs). 472 aminoadicic residues. To this receptor is bound to N-arachidonoylethanolamide, its internal ligand, THC the main component of marijuana and other agonits and antagonist. The molecular structure comes from mathethics aproximations.

CB1 is also unusual, even among GPCRs, in that its internal ligand, anandamide, is synthesized from lipid, a fat-like material in the cell membranes. Most ligands of GPCRs are water soluble and approach the receptor from outside the cell.

Anandamide interacts with transmembrane helix 6 TMH6, it moves the helix “kicks out” to the side, changing the protein conformation. View video 3d simulated animation of retrograde neuronal signaling mediated by cannabinoid receptor.

Hypotetical cannabinoid receptor CB1 binding to anandamide.

Modelo del receptor cannabinode humano CB1. Partiendo de la base de la estructura del rodopsina 2z73a y calculando comparativamente con la secuencia de aminoácidos de ambos, se llega a una estructura tridimensional. El 3D lo podemos encontrar en modBase que es una base de datos de modelos de proteínas calculados por modelado compartivo.

Simulaciones por ordenador llevadas a cabo en el Pittsburgh Supercomputing Center apuntan que la anandamida puede unirse al receptor CB1 como de forma parecida a como se muestra en la figura. Parece ser que la anandamida se encuentra fundamentalmente en su forma extendida dentro del receptor. Interaccionando en su parte más baja con una valina V3.43 y una isoleucina I6.46 de la hélice transmembrana 6 TM6. K3.28

Aminoacidic sequence of complete protein with residues calculated in modelization in green.

Patricia H. Reggio, Computational Methods in Drug Design: Modeling G Protein-Coupled Receptor Monomers, Dimers, and Oligomers. AAPS Journal. 2006; 8(2): E322-E336.