Fig. 4: The unconventional activation mechanism of GAL1R and GAL2R.
From: Molecular basis for allosteric agonism and G protein subtype selectivity of galanin receptors
a Structural comparison of GAL1R-Gi and GAL2R-Gq complexes with μOR in the inactive state (PDB: 6DKL). The outward movement of TM6 and inward shift of TM7 in galanin receptors relative to μOR are shown as red arrows, indicative of the fully active conformation of both galanin receptors. b Three positively charged residues involved in agonism signaling transmission of galanin in GAL1R (left panel) and GAL2R (right panel). c Sequence alignment of residues at 6.51, 7.35, and 7.39 in class A peptide GPCRs. The effects of mutation of three positively charged residues on galanin-induced activation of GAL1R (d) and GAL2R (e). WT and receptor mutants were transfected into HEK293/Gα16 cells and intracellular calcium response was measured to reflect the activity of galanin. Data shown are mean ± S.E.M. of six independent experiments (n = 6). Source data are provided as a Source Data file. f–i The conformational rearrangement of residues in conserved “micro-switches” upon galanin receptors activation. In contrast to μOR in the inactive state, the conformational changes of “micro-switches” residues in toggle switch (f), PIF (g), DRY (h), and NPxxY (i) of GAL1R and GAL2R are indicated as red arrows. The movement of TM6 and TM7 are highlighted as red arrows.
