9.A.14.3.9
The dopamine receptor D3, DRD3 or D3R of 400 aas.  Residues involved in receptor signaling have been identified (Kota et al. 2015), and several agonists are known (Xu et al. 2016). The atomic-level dopamine activation mechanism for transmitting extracellular ligand binding events through transmembrane helices to the cytoplasmic G protein has been elucidated (Weng et al. 2017). In agonist-bound systems, the D3R N-terminus forms a "lid-like" structure and lies flat on the binding site opening, whereas in antagonist-bound systems, the N-terminus exposes the binding cavity. A continuous water pathway is present only in the dopamine-Galphai-bound system. In the inactive D3Rs, water entry is hindered by the hydrophobic layers. It was proposed that upon agonist binding, the "lid-like" conformation of the N-terminus induces a series of molecular switches to increase the volume of the D3R cytoplasmic binding part for G protein association. Water enters the transmembrane region, inducing molecular switches to assist in opening the hydrophobic layers to form a continuous water channel, which is crucial for maintaining a fully active conformation for signal transduction (Weng et al. 2017). S-Deoxyephedrine can move through molecular channels within D3R (Li et al. 2017).