Extended Data Fig. 6: Effects of mutations of key residues of MRGPRX2 on polycationic compound drugs induced MRGPRX2 activation.
From: Structure, function and pharmacology of human itch receptor complexes
a, Effects of mutations of key residues of MRGPRX2 on polycationic compound drugs induced MRGPRX2 activation via Gαi–Gγ dissociation assay. The SNP mutations were highlighted in blue. ND, not detectable due to low signal. Data from three independent experiments are presented as the mean ± SEM (n=3). (Atracurium: P =0.0018, 0.0013, ND, ND, < 0.0001, ND, 0.0064, ND from top to bottom. Tubocurarine: P =0.0003, 0.0013, 0.0037, ND, 0.0064, < 0.0001, < 0.0001, ND from top to bottom. Ciprofloxacin: P < 0.0001, 0.0003, ND, 0.0006, ND, ND, 0.0267, 0.0012 from top to bottom. Rocuronium: P =0.0410, 0.0132, ND, ND, ND, 0.0078, 0.9383, ND from top to bottom). b, Effects of mutations of key residues of MRGPRX2 on polycationic compound drugs induced MRGPRX2 activation via Gαq–Gγ dissociation assay. The SNPs were highlight in blue. Values are the mean ± SEM of three independent experiments for the wild type (WT) and mutants (n=3) except values of E164A and W243R in the ligand Ciprofloxacin, values of F170A, D184A, D184H, W243A and W243R in the ligand Rocuronium are the mean ± SEM of five independent experiments (n=5). (Atracurium: P < 0.0001, < 0.0001, 0.0181, 0.0010, 0.0013, < 0.0001, < 0.0001, < 0.0001 from top to bottom. Tubocurarine: P < 0.0001, < 0.0001, 0.0002, 0.0021, < 0.0001, 0.0056, 0.0004, < 0.0001 from top to bottom. Ciprofloxacin: P < 0.0001, 0.0001, < 0.0001, < 0.0001, < 0.0001, < 0.0001, 0.0007, < 0.0001 from top to bottom. Rocuronium: P < 0.0001, < 0.0001, < 0.0001, < 0.0001, 0.0020, < 0.0001, < 0.0001, < 0.0001). a-b, Upper panel, bar graph representation of pEC50. Lower panel, dose response curves. Statistical differences between WT and mutations were determined by two-sided one-way ANOVA with Tukey test. *, P < 0.05; **, P < 0.01; ***, P < 0.001, n.s., no significant difference.
