Fig. 6: The diverse activation mechanisms of class A GPCRs.
From: Structural basis for chemokine receptor CCR6 activation by the endogenous protein ligand CCL20
a Proposed model of CCR6 activation by CCL20. In the absence of CCL20, the noncanonical toggle switch Q6.48 is involved in an H-bond network that stabilizes CCR6 in an inactive state. Binding of CCL20 is associated with the disruption of these interactions, facilitating CCR6 activation and downstream G protein coupling. The salt bridge between the N-terminal NH3+ group of CCL20 and the CCR6-specific side-chain E45.51 from ECL2 is illustrated in the cartoon. b Activation mechanism of the M2 receptor as demonstrated by previous structural studies. The canonical toggle switch W6.48 adopts a different rotamer conformation when agonist is bound, which is the key trigger for M2 activation and downstream G protein coupling. The active state of M2 has a smaller extracellular pocket which is utilized by a PAM, LY2119620. The CCL20-binding site in CCR6 resembles the shallow PAM-binding site observed in M2.
