Extended Data Fig. 10: Potential structural mechanism of SPE recognition among TAAR members.

a, Dose response curves of Gαs-Gβγ dissociation in receptor (mTAAR1-6, 7d, 8c, and 9)-overexpressing HEK293 cells in response to stimulation with SPE. Values are represented as mean ± SEM of 3 independent experiments (n = 3). b, The average RMSD value of SPE (upper panel) and binding site residues in SPE-mTAAR5 complex during triplicate 200 ns MD simulations. The overall MD simulated structure was shown in Supplementary Fig. 14b. We built the coordinates of mTAAR5 using our solved mTAAR9 structure as a template via SWISS-MODEL. c, 3D representation of the detailed interactions between SPE and D114^3.32, Y295^7.34 residues of mTAAR5. d-e, Dose response curves of key residue mutations in the polyamine recognition pocket of mTAAR9 (d) and mTAAR5 (e) in response to stimulation with SPE. Values are represented as mean ± SEM of 3 independent experiments (n = 3). f, Structural representation of the potential effects of structurally equivalent mutations of mTAAR6, mTAAR7d, and mTAAR8c. Conserved interactions of in the polyamine recognition pocket (T^3.29 and T113^3.33) were mimicked by generating mutations of V113^3.33 to T in mTAAR6, S124^3.39 and G128^3.33 to T in mTAAR7d, and S108^3.29 and V112^3.33 to T in mTAAR8c. g, Dose response curves of HEK293 cells overexpressing mTAAR6, mTAAR7d, mTAAR8c, and the indicated mutants in the polyamine recognition pocket according to Fig. 4f in response to SPE stimulation. Values are represented as mean ± SEM of 3 independent experiments (n = 3).