Fig. 5: Mutating Y271^6.51 leads to differential loss of signaling.

a Stimulation of CXCR3^Y271A (blue) with either VUF10661 or VUF11418 induces G-protein signaling to a similar extent as wild-type receptor (black) when measured using a cAMP response assay, and reduced G-protein dissociation. Stimulation of CXCR3^Y271A with VUF10661 and VUF11418 leads to a drastic loss in βarr1 recruitment. Data (mean ± SEM) represents either three (for G-protein assays) or four (for βarr1 recruitment) independent experiments, performed in duplicate, and has been normalized with respect to the signal observed at the lowest ligand concentration, treated as either 100% (for G-protein assays) or 1 (for βarr1 recruitment). b Y271^6.51 adopts a similar orientation and contacts the ligand in both VUF11418 and VUF10661-bound CXCR3 structures. (VUF10661-CXCR3: olive drab, VUF10661: cyan, VUF11418-CXCR3: pale violet red, VUF11418: deep teal). Source data are provided as a Source Data file.