Figure 2.
Smoothened (SMO) as a model for FZD receptor structure. (A) Structure of smoothened extracellular and transmembrane domains (TMDs), showing an extracellular extension of transmembrane helix 5 and a partially structured CRD‐to‐TMD linker which closes off the sterol‐binding pocket with bound cholesterol (shown in red spheres). (B) Comparison of palmitoyl coordination in FZD4 receptor CRD and cholesterol coordination in smoothened. (C) Available crystal structures of FZD receptor CRDs aligned to show structural similarity. (D) Graph of overall sequence proportion in each smoothened domain shared with FZD family members. Total conservation was calculated from 50% gap‐trimmed multiple sequence alignment of hSMO with all hFZDs and averaged for all residues in a given topology or domain.