Fig. 10: Activation and inhibition of TRPV2 by various ligands.
From: Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function
The vanilloid pocket of ligand-free TRPV2 is occupied by lipids and demonstrates auto-stimulation of the selectivity filter (SF, or upper gate), as observed in-between two TRPV2 apo structures (TRPV2apo-1, PDB-ID: 6U84 and TRPV2apo-2, PDB-ID: 6U86). Two ligand-dependent activating mechanisms of TRPV2 are displayed. The presence of C16, probenecid, 2-APB (PDB-ID: 7T37) or RTX (PDB-ID: 6OO7) at different locations in TRPV2 displace the lipid from the vanilloid pocket (note: RTX only activates a modified TRPV2 form). In contrast, CBD (PDB-ID: 6U8A and 6U88) is unable to repel the lipid from the vanilloid pocket. PLG (PDB-ID: 6WKN) inhibition is achieved via the replacement of the lipid in the vanilloid pocket. The arrows indicate approximate molecular shifts.
