Extended Data Fig. 3: Dynamics of helix V and VI in FZD4 and a comparison of the intracellular side of FZD4 with other GPCRs.
From: Crystal structure of the Frizzled 4 receptor in a ligand-free state
a, Cα r.m.s.d. for residues G409 to S418 (helix V) and R432 to S441 (helix VI) plotted as a rolling average over a 10-ns window. b, Unique hydrogen bonds between helix III and helix VI (W3203.43f–S4116.37f and W3273.50f–M4346.30f) maintain helix VI in an inward conformation. c, The intracellular cavity of FZD4 is close to W7.55f and the KTXXXW motif (coloured in dark grey), a region that is key for downstream signalling. Compared with class-A GPCRs (adenosine A2A and β2 adrenergic receptors), FZD4 leaves no cavity among helices III,VI and VII, whereas SMO has a side-pocket at this position. R3.50 (labelled with a blue sphere) is a key residue in the activation of class-A GPCRs and is exposed to the intracellular surface. The residue in the same position in class-F, W3.50f, points in a different direction and is not exposed. The G-protein-binding sites of class-A GPCRs are labelled in red.
