Extended Data Fig. 8: GTP-bound Gαs in the β₂AR-Gs complex transitions to a similar structure as activated Gαs-GTPγS.

a-g, Structures comparing the overall architecture of the first and last frames of the β₂AR-Gs^EMPTY and β₂AR-Gs^GTP trajectories with ‘checkpoint’ crystal structures of nucleotide free β₂AR-Gs complex PDB:3SN6 and activated Gαs-GTPγS. Models are aligned to the RHD. h, Rotation of Gs in relation to receptor (aligned) over structures of β₂AR-Gs^GTP cryo-EM structural transition frames. i, Placement of α5 Phe in relation to hydrophobic pocket on RHD β-sheets. Rendering style inspired by Jang et al.¹⁹. The residue F376 of Frame 20 ( + GTP condition), in the bottom-middle panel, is translucent blue to indicate it has been built in as a likely position but is stubbed in our deposited molecular model of that frame. j-k, The transition state of US28-G11^GDP captured in the process of nucleotide release is similar to that of β₂AR-Gs^GTP (frame 20). l-m, Trace of the root-mean-square-deviation (RMSD) over the 20 β₂AR-Gs^GTP structural transition frames. Structures have been aligned to the rigid elements of the Gαs-RHD, and the RMSD has been computed both for the Cα atoms of the whole Gαs-RHD (l) and just of the α5 helix (m). The traces show that for both the Gαs-RHD as a whole and the α5 helix, the early frames are structurally closer to PDB:3SN6, whereas the last three frames, from 18 onwards, are closer to PDB:1AZT.