Fig. 4: Activation mechanisms of peptide-binding class A GPCRs.
a Left: active structure of the Sar1-angiotensin II‒AT1R‒Gq complex (PDB: 7F6G), color-coded as follows: Sar1-Angiotensin II (pink), AT1R (green), Gαq (cyan), Gβ (orange) and Gγ (magenta). Middle: structural comparison of the active (green, PDB: 6OS0) and inactive (gray, PDB: 4YAY) states of AT1R. Right: close-up view of the binding pocket highlighting the critical role of the C-terminal phenylalanine (F8) of angiotensin II in receptor activation. Conformation changes in key residues are indicated by green arrows, while the red arrow marks the outward movement of TM6 upon activation. b Left: active structure of CCR5 (yellow), in complex with CCL5 (slate) and the Gi heterotrimer (Gαi (salmon), Gβ (orange), and Gγ (magenta)) (PDB: 7O7F). Middle: structural comparison between the active (yellow, PDB: 7O7F) and inactive (gray, PDB: 6AKY) states of CCR5. Right: close-up of the orthosteric pocket showing how the N-terminal region of CCL5 interacts with the receptor. Upon activation, conformational changes in W2486.48 and the outward movement of TM6 are indicated by yellow and red arrows, respectively. c Left: active structure of MOR (cyan) in complex with endomorphin (blue) and the Gi heterotrimer (PDB: 8F7R). Middle: structural comparison between the active (cyan, PDB: 8F7R) and inactive (gray, PDB: 4DKL) states of MOR. Right: close-up of the orthosteric pocket showing the binding of Y1 of endomorphin (blue). The red arrow highlights the outward movement of TM6 during activation.
