Crystal Structure of the Human Cannabinoid Receptor CB2.
The first high-resolution structure of the cannabinoid receptor 2 (CB2) shows how different drug molecules work on different parts of the endocannabinoid pathway.
A ShanghaiTech University–led team determined the crystal structure of CB2 in complex with a molecule designed to block the receptor.
The researchers showed that CB1, a receptor widely distributed in the central nervous system, and CB2, a receptor predominately expressed in the immune system, have distinct interaction sites for antagonistic drugs.
However, the structure of the binding pocket for antagonists of CB2 resembled that of the binding pocket for activating agents of CB1, which helps explain why substances stimulating one receptor can weaken or inhibit the other, and vice versa.
The findings should help scientists better understand the effects of cannabis, the components of which act on CB1 and CB2. The new structure should also enable more rational and selective drug design for desired therapeutic effects.
- Cell 176, 459–467.e13 (2019). doi: 10.1016/j.cell.2018.12.011