Supplementary Fig. 5: Structural comparison of DRPB_Fz4-Fz4 and DRPB_Fz8-Fz8.
From: Receptor subtype discrimination using extensive shape complementary designed interfaces
a, Superposition of the overall structures of the DRPB_Fz4-Fz4CRD and DRPB_Fz8-Fz8CRD showing backbone movement of DRPB_Fz4 (light green), but the original designed “fingers in groove” binding mode is retained. The two complexes were aligned by aligning the Fz4CRD (salmon) with Fz8CRD (light blue), with RMSD of 1 Å. DRPB_Fz8 is colored in light orange. There is no electron density for the C-terminal part of DRPB_Fz4 (residues 160–190), therefore this part of DRPB_Fz4 is not built and shown in the figure. b, Superposition of the overall structures of the DRPB_Fz4-Fz4CRD with XWnt8-Fz8CRD (PDB:4F0A). The two complexes were aligned by aligning the Fz4CRD with Fz8CRD. XWnt8 is colored in magenta. The lipid group of XWnt8 is sterically clashing with DRPB_Fz4 “fingers”. c, Representative zoomed view of Met9Arg mutation. This Met to Arg mutation in DRPB_Fz4 allows hydrogen bond and salt bridge formation with Asp74 of Fz4. d, Zoomed view of Ala101Phe mutation in DRPB_Fz4. Phe101 sidechain is deeply buried in the hydrophobic groove, conferring affinity. On the other hand, in DRPB_Fz8 the Ala101Phe mutation prevents the overall geometry adopted by DRPB_Fz8, eliminating Fz8 subtype binding. e, The loop regions of Fz4CRD interact with each other and adopt a usual dimer geometry within the crystal packing. The dimeric FzCRDs are colored in salmon and light yellow, respectively. Such dimer is not observed for the other DRPB-CRD complexes.
