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. Author manuscript; available in PMC: 2020 Apr 19.
Published in final edited form as: Annu Rev Pharmacol Toxicol. 2017 Oct 2;58:429–449. doi: 10.1146/annurev-pharmtox-010617-052933

Figure 2. Models of the activation of adhesion GPCR signaling.

Figure 2.

Generally speaking, adhesion GPCR activation is governed by interactions between the N-terminal fragment (NTF) and C-terminal fragment (CTF) protomers. A) The tethered agonist (e.g. stalk, stachel) can be unmasked when the NTF is completely removed. B) The stalk may also act as a lever, with its position being modulated by NTF movements to tune receptor activity. C) The NTF can also in some cases suppress signaling by the CTF protomer in ways that do not depend on the stalk, with disinhibition being achieved when the NTF is pulled away from the CTF by ligand interactions or shed completely from the protein complex. It should be noted that these mechanisms are not mutually exclusive, and in fact all three mechanisms may occur for any given aGPCR, although the relative importance of each mechanism may vary from receptor to receptor.