Extended Data Fig. 8: The similarity and the difference of PTH1R in G protein-coupling by hormone peptide and small molecule agonist.
From: Conserved class B GPCR activation by a biased intracellular agonist
(a) Structural comparison of G protein in different ligands bound PTH1R-Gs complex structures. (b) Close up of the αN and Gαs-α5 helix of Gαs, which form interactions with ICL2 and TMD helix bundles in all G protein bound complex structures, showing similar G protein conformation, but the noteworthy difference is that the C-terminal of Gαs-α5 helix makes additional interactions with the small molecule agonist. (c) Good cryo-EM density supports ligand interact with Gαs. (d-f) The similar set of interactions between the C-terminal of Gαs-α5 helix with the receptor. E392 shifts outward due to steric clash. Y391, E392, and L393 form additional interactions with PCO371.
