Figure 2.

Eight phenotypes of MT₂ variants and their localization in the receptor sequence. (a) Superimposition of signaling signatures sharing the same cluster for the eight clusters. Basal activities (BA), agonist-mediated maximal efficacies (M), and Δlog(τ/K_A) ratios (ΔTC)⁵¹ were expressed as normalized differences from WT MT₂. (b) Localization of the 40 MT₂ variants color-coded according to their respective cluster (CL): red (CL1; severe global signaling impairment), orange (CL2; moderate global signaling impairment), yellow (CL3; slight global signaling impairment), purple (CL4; selective impairment of agonist-mediated βarr2 recruitment), light blue (CL5; selective impairment of Gα_i1 activation and basal βarr2 recruitment), dark blue (CL6; Gα_i1 activation selective impairment), green (CL7; Gα_z activation selective impairment), and black (CL8; no signaling impairment). * indicates the four variants that lose the ability of binding melatonin. The snake plot was created using the tools at www.gpcrdb.org.