Extended Data Fig. 9: Sequence alignment of human TAAR family, TAAR1 activation mechanism, and analysis of METH binding in human and rodent TAAR1.
From: Recognition of methamphetamine and other amines by trace amine receptor TAAR1
(a-b) Sequence alignment of residues important for TAAR1-ligand binding (a) or activating (b) from human TAAR family and mTAAR9. (c-d) Superposition of activated TAAR1 (dark cyan) with active mTAAR9 (light green; PDB ID: 8iw7), β2AR (orange; PDB ID: 6kr8) and inactive β2AR (gray; PDB ID: 5jqh). Notable conformational changes occur at extracellular end of TM1 and intracellular ends of TM6, TM7 and H8 upon receptor activation, side view (c) and bottom view (d). (e) The “toggle switch”, W2646.48, of TAAR1 display relative rotameric change when sensing agonist. (f–h) The key P-I-F6.44 (f), D-R3.50-Y (g), and N-P7.50-xx-Y7.53 (h) motifs displayed conformational rearrangement in activated TAAR1 structure. (i–k) RMSD plot of METH binding in rat, mouse, or human TAAR1 pocket during simulations. (l) Bar graph showing RMSD differences for METH binding in rat, mouse, or human TAAR1 pocket during simulations. Data are mean ± S.E.M. of RMSD from 3 independent experiments (n = 3) for rat and mouse TAAR1 and 6 independent experiments (n = 6) for human TAAR1. (m) Sequence alignment for residues that are important for ligand binding to TAAR1 from rat, mouse or human.
