Fig. 7: Role of conserved tyrosines Y^5.58 and Y^7.53 in the activation of β₁AR.

a ¹H-¹⁵N TROSY spectra of ¹⁵N-valine-labeled YY-β₁AR in the binary complex with isoprenaline (blue) and in the ternary complex with isoprenaline and Nb80 (orange) at 21 T. Resonances are marked with assignment information. Green lines connect resonances corresponding to the major (preactive) and minor (active) conformation in the binary isoprenaline complex where the resonances of the minor conformation coincide with the ternary complex. Assignments marked by asterisks are tentative for the ternary complex. The minor V314 resonance of the YY-β₁AR•isoprenaline complex was only observed in a spectrum recorded at 14 T (Fig. 6). b Structure of β₁AR in complex with isoprenaline (2Y03). Valines are shown as spheres color-coded according to the spectral observation in a. Green: minor conformation observed in the binary YY-β₁AR•isoprenaline complex, which coincides with the ternary YY-β₁AR•isoprenaline•Nb80 complex. Blue: no second conformation observed in the binary complex. Black: no change between binary and ternary complex. Gray: no assignment available in the ternary complex. c, d Bottom and side view of tyrosines Y^5.58 and Y^7.53 in the structures of β₂AR in a binary antagonist complex (2RH1, c) and a ternary agonist•Nb6B9 complex (4LDE, d). Y^5.58, N^7.49, P^5.50 and Y^7.53 are depicted as sticks (CPK-yellow). Water molecules involved in H-bonds with Y^5.58 and Y^7.53 are shown as red spheres. Helices TM5, TM6, TM7 and Nb6B9 are indicated by different colors. e Conservation of Y^5.58 and the NPxxY^7.53 motif within all 1554 class A GPCR entries in the GPCRdb⁵⁹. Source data are provided as a Source Data file.