Fig. 4: Activation mechanism of NMURs.
From: Structural insights into the peptide selectivity and activation of human neuromedin U receptors
a Structural superposition of active NMUR2 and antagonist-bound ghrelin receptor (PDB 6KO5) from the side view. The movement directions of TMs in NMUR2 relative to the ghrelin receptor are highlighted as black arrows. NMUR2 and ghrelin receptor are colored in hot pink and wheat, respectively. b Interactions between NMU and residues located at the bottom of peptide binding pocket. c Comparison of interaction between peptide and R6.55. The possible clash is highlighted by a red dashed circle. Hydrogen bonds and salt bridges are depicted as orange dashed lines. Compound 21, the antagonist of ghrelin receptor, and NMU are colored in grey and green, respectively. d–g Conformational changes of the conserved “micro-switches” upon receptor activation, including Toggle switch (d), ERY (e), PIF (f), and NPxxY (g) motifs. The conformational changes of residue side chains are shown as black arrows upon NMUR2 activation in contrast to the antagonist-bound ghrelin receptor.
