Fig. 6: Activation and inactivation mechanisms of FFA2.
From: Structural insights into lipid chain-length selectivity and allosteric regulation of FFA2
a Superimposed images of active (purple) and inactive (beige) FFA2. The dashed squares indicate the regions of the views in (b–g). The eye and arrow symbols indicate the angle of the views in (e–g). The black arrows indicate the conformational changes of the TM helices between the active and inactive states of FFA2. b–e Enlarged views of the active and inactive states of FFA2. b The rearrangement of the orthosteric binding site. c, d The shift of extracellular sides of TM6 (c) and TM7 (d). e Collapse of the sodium pocket. Black arrows indicate the downward shift of the transmembrane helices or conformational changes of the side chains. Hydrogen bonds are represented as dashed black lines. f, g Top views of the active and inactive states of TM6 (f) and TM7 (g). The black arrows indicate the rotation of the transmembrane helices. h A model of FFA2 activation induced by orthosteric agonists. The black arrows indicate the conformational change of the helices and key residue (N2306.43) between the inactive and active FFA2. i A model of FFA2 inactivation induced by the allosteric antagonist, GLPG0974. The red and green dashed circles indicate the orthosteric site and the allosteric site 1, respectively. j A model of FFA2 activation induced by the allosteric agonist, 4-CMTB. The straight black arrow and curved black arrows indicate the ligand access pathway and the flexibility in TM6 and TM7 of FFA2, respectively. The blue dashed circle indicates the allosteric site 2.
