Extended Data Fig. 9: Structural comparison of G_q-coupled MRGPRX2 and MRGPRX4.

a–d, Structural comparison of the MRGPRX4-G_q-MS47134 complex with the MRGPRX2-G_q-(R)-ZINC-3573 complex. The receptor and G_q protein of MRGPRX4-G_q complex are colored by green and blue, respectively. The receptor and G_q protein of MRGPRX2-G_q complex are colored by cyan and salmon, respectively. Side view (a), Close-up view of αN-ICL2 interaction region (b), α5 helix region (c), and the cytoplasmic side of receptors (d). e, The acidic residues E157^4.60 and D177^5.38 of MRGPRX4 are shielded by the inserted ECL2. Side chain of D177 is not resolved but modeled here for a better visual interpretation. f, Residues E164^4.60 and D184^5.38 of MRGPRX2 extend to the cationic agonists accessible pocket. g, Due to the variance in residue 2.39, Y243^H5.23 of G_q adopts different side-chain conformations to interact with Y130^ICL2 of MRGPRX4 and Y137^ICL2 of MRGPRX2. h, i, BRET2 G_q assays for Y130^ICL2A of MRGPRX4 (h) and Y137^ICL2A of MRGPRX2 (i). Data represent mean ± s.e.m. of n = 3 biological replicates.