Fig. 5. Activation mechanism of H₄R.

a Activation motifs in the H₄R structure. Each motif residue is shown as a blue stick. b–g Structural comparison between the active H₄R_ime (blue) and antagonist-bound inactive H₁R_his (gray, PDB 3RZE). (b) CwxP motif, (c) PI(V)F motif, (d) DR(E)Y motif, (e) NPxxY motif. Imetit and doxepin are shown as magenta and khaki sticks. The residues involved in receptor activation are indicated by sticks, and conformational changes are shown as red arrows. Microswitch rearrangement allowed movement outside the cytoplasmic ends of TM5 and 6 (f). g Gln347^7.42 coordination and its effect on surrounding residues.