Figure 5

Schematic illustration of ligand-binding process of TAAR9. Firstly, the negative-charged glutamates in ECL2 attract the positive-charged amine to approach the opening of tunnels in the receptor (top). Then the amine ligand can enter either vestibular binding pocket 1 through Tunnel 1 (green) interacting with D^6.58 (middle left), or vestibular binding pocket 2 through Tunnel 2 (yellow) interacting with E^7.36 (middle right). Both tunnels lead to the orthosteric binding pocket, where the amine ligand can bind firmly with D^3.32 and gets stabilized with surrounding residues having aromatic rings (bottom).