Fig. 4: Structural comparison between active and inactive MC4R.
From: Structure elucidation of a human melanocortin-4 receptor specific orthosteric nanobody agonist
a, b Side views of the overlay (MC4R receptor only) of the SHU9119-bound (dark blue), inactive state MC4R structure (gray, PDB ID 6W25) with the setmelanotide- (orange, 7PIU) or pN162-bound (cyan, 8QJ2) active state MC4R structures (receptor in pink and purple, respectively). c Bottom view of the same overlay showing the hallmark TM6 outward and the TM5 inward movement upon receptor activation (indicated with arrows). d Top view of the same 6W25-7PIU-8JQ2 overlay. e MIF motif rearrangement and impact on W2586.48 of the CWxP toggle switch motif and L1333.36. f D/NPxxY and ionic lock DRY motif rearrangements upon activation and its impact on residues Y2125.58 and Y3027.53. Side chain rearrangements between inactive and active states are indicated with arrows.
