Extended Data Table 1 Influence of gradient transfection of \({{\bf{GEM}}}_{{\bf{anchor}}}^{{\bf{TM1}}{\boldsymbol{/}}{\bf{2}}{\boldsymbol{/}}{\bf{4}}}\), \({{\bf{GEM}}}_{{\bf{BAM}}}^{{\bf{TM3}}{\boldsymbol{/}}{\bf{4}}{\boldsymbol{/}}{\bf{5}}}\), and \({{\bf{GEM}}}_{{\bf{NAM}}}^{{\bf{TM5}}{\boldsymbol{/}}{\bf{6}}{\boldsymbol{/}}{\bf{7}}}\) on cAMP accumulation and β-arrestin 2 recruitment mediated by D1R

From: De novo design of GPCR exoframe modulators

  1. aGloSensor results of cAMP accumulation for D1R (WT and GEM binding) and BRET assay of β-arrestin 2 recruitment were normalized to the maximal response of WT D1R without GEM. Data are presented as means ± SEM from at least three independent experiments performed in technical triplicate. NSP > 0.05, *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001 by one-way ANOVA followed by Dunnett’s post-test compared with WT D1R (P > 0.9999, > 0.9999, > 0.9999, > 0.9999, > 0.9999 from top to bottom for pEC50 in the cAMP accumulation assay of \(\text{GE}{\text{M}}_{\text{anchor}}^{\text{TM}1/2/4}\); P > 0.9999, > 0.9999, > 0.9999, > 0.9999, > 0.9999 from top to bottom for pEC50 in the β-arrestin 2 recruitment assay of \(\text{GE}{\text{M}}_{\text{anchor}}^{\text{TM}1/2/4}\); P > 0.9999, > 0.9999, > 0.9999, = 0.8298, > 0.9999 from top to bottom for pEC50 in the cAMP accumulation assay of \(\text{GE}{\text{M}}_{\text{BAM}}^{\text{TM}3/4/5}\); P > 0.9999, > 0.9999, > 0.9999, > 0.9999, > 0.9999 from top to bottom for pEC50 in the β-arrestin 2 recruitment assay of \(\text{GE}{\text{M}}_{\text{BAM}}^{\text{TM}3/4/5}\); P = 0.7303, > 0.9999, = 0.8272, = 0.0178, <0.0001 from top to bottom for pEC50 in the cAMP accumulation assay of \(\text{GE}{\text{M}}_{\text{NAM}}^{\text{TM}5/6/7}\); P > 0.9999, > 0.9999, = 0.9946, = 0.0233, > 0.9999 from top to bottom for pEC50 in the β-arrestin 2 recruitment assay of \(\text{GE}{\text{M}}_{\text{NAM}}^{\text{TM}5/6/7}\); P > 0.9999, > 0.9999, = 0.9312, > 0.9999, > 0.9999 from top to bottom for efficacy in the cAMP accumulation assay of \(\text{GE}{\text{M}}_{\text{anchor}}^{\text{TM}1/2/4}\); P > 0.9999, > 0.9999, > 0.9999, = 0.9292, = 0.0480 from top to bottom for efficacy in the β-arrestin 2 recruitment assay of \(\text{GE}{\text{M}}_{\text{anchor}}^{\text{TM}1/2/4}\); P > 0.9999, = 0.8096, > 0.9999, = 0.4090, = 0.2871 from top to bottom for efficacy in the cAMP accumulation assay of \(\text{GE}{\text{M}}_{\text{BAM}}^{\text{TM}3/4/5}\); P = 0.2503, <0.0001, <0.0001, <0.0001, <0.0001 from top to bottom for efficacy in the β-arrestin 2 recruitment assay of \(\text{GE}{\text{M}}_{\text{BAM}}^{\text{TM}3/4/5}\); P > 0.9999, = 0.0242, <0.0001, = 0.1617, = 0.0097 from top to bottom for efficacy in the cAMP accumulation assay of \(\text{GE}{\text{M}}_{\text{NAM}}^{\text{TM}5/6/7}\); P < 0.0001, <0.0001, <0.0001, <0.0001, <0.0001 from top to bottom for efficacy in the β-arrestin 2 recruitment assay of \(\text{GE}{\text{M}}_{\text{NAM}}^{\text{TM}5/6/7}\)).
  2. bThe efficacy is defined as the window between the maximal response (Emax) and the vehicle (no agonist).
  3. cThe Surface expression ratio is defined as the proportion of D1R or GEM present on the cell surface relative to its total cellular amount.
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