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. Author manuscript; available in PMC: 2021 Jul 4.
Published in final edited form as: Nat Chem Biol. 2021 Jan 4;17(3):291–297. doi: 10.1038/s41589-020-00702-5

Fig. 5: Schematic of the stepwise activation model for mGluR2.

Fig. 5:

Four-state stepwise model for the mechanism of allosteric activation of mGluRs with receptors shown in green and ligand in red. Darker shading of CRDs and TMDs represent greater occupancy of a given conformation. State 1 (FRET=0.31) represents the most common CRD conformation of an unliganded receptor, where the CRDs are farthest apart. State 2 (FRET=0.51) represents the CRD conformation resulting from ligand binding to a single VFT domain. State 3 (FRET=0.71) represents the CRD conformation resulting from ligand binding to both VFT domains and prior to the formation of a stabilizing TMD interaction. State 4 (FRET=0.89) represents the CRD conformation resulting from ligand binding to both VFT domains and a stabilizing TMD interaction. State 4 is the active conformation of the receptor. PAM mutations can function by increasing transitions from state 3 to 4.