Supplementary Figure 5: 5-HT_2BR structure and function by LY266097.

a,5-HT_2BR–LY266097 structure F_o – F_c omit map of ligand (left), 2F_o – F_c regular map of ligand (middle) and binding pocket residues (right). b, F_o – F_c omit density map of residues T140^3.37 and L362^7.35 in the 5-HT_2BR–LY266097 structure. c, LY266097 5-HT_2BR G_q-mediated PI hydrolysis (EC₅₀ = 3.6 nM, E_max = 52%). Data are expressed as percent 5-HT response and represent means ± s.e.m. from three independent experiments (n = 3) performed in duplicate. d, LY266097 β-arrestin2 recruitment as measured by BRET¹ over 5, 30, 60 and 120 min. Data represent means ± s.e.m. from two independent experiments (n = 2) performed in duplicate and are expressed as percent 5-HT NET BRET ratio response. e, β-arrestin2 recruitment as measured by Tango comparing agonist activity of 5-HT (black, EC₅₀ = 11 nM) to LY266097 (blue, closed circles), where LY266097 exhibits β-arrestin2 recruitment antagonism (blue, open circles, IC₅₀ = 2.2 nM) of 5-HT. Data represent means ± s.e.m. from two independent experiments (n = 2) performed in triplicate and are expressed as percent 5-HT response.