Serotonin Receptor 5-HT1A DMT Complex 7E2Y

Serotonin, or 5-hydroxytryptamine (5-HT), is an important neurotransmitter 1,2 that activates the largest subtype family of G-protein-coupled receptors 3 . Drugs that target 5-HT 1A , 5-HT 1D , 5-HT 1E and other 5-HT receptors are used to treat numerous disorders 4 . 5-HT receptors have high levels of basal activity and are subject to regulation by lipids, but the structural basis for the lipid regulation and basal activation of these receptors and the pan-agonism of 5-HT remains unclear. Here we report five structures of 5-HT receptor-G-protein complexes: 5-HT 1A in the apo state, bound to 5-HT or bound to the antipsychotic drug aripiprazole; 5-HT 1D bound to 5-HT; and 5-HT 1E in complex with a 5-HT 1E - and 5-HT 1F -selective agonist, BRL-54443. Notably, the phospholipid phosphatidylinositol 4-phosphate is present at the G-protein-5-HT 1A interface, and is able to increase 5-HT 1A -mediated G-protein activity. The receptor transmembrane domain is surrounded by cholesterol molecules-p