Residue-level mapping of E1ExP5-triggered conformational transduction. (A) TM5–TM6 collective displacements toward the cytoplasmic end as compared with the apo GLP-1R structure. (B) Depiction of TM6–Gα5 coupling, which involves multiple SBs and H-bond anchors at the C-terminus of the Gα5 helix. (C) Depiction of TM5–Gαs coupling, including (left) comparison with the apo structure showcasing the critical movement of ICL3 and (right) detailed description of the anchors involved in the Gs protein coupling. (D, E) Structure rearrangement of the heterotrimeric Gs protein in the absence of Nb35. The cryo-EM structure of the ExP5–GLP-1R–Gs complex (PDB code: 6B3J),13 which was stabilized by Nb35 during determination, is used here for comparison.