Figure 7. Modelling of a ternary 2:2:2 LGR_ecto–Rspo_Fu1–Fu2–ZNRF3_ecto complex and its implication for signalling.

(a) The hLGR5_ecto × hRSPO1_Fu1–Fu2 × mZNRF3_ecto 2:2:2 complex was generated by superposing the ternary hLGR5_ecto × RSPO1_Fu1–Fu2 × hRNF43_ecto complex25 (Protein Data Bank ID code 4KNG) onto the mZNRF3_ecto dimer from the mRSPO2_Fu1–Fu2 complex. No clashes are observed. Glycosylation sites of LGR5 all point into the periphery of the shown complex. (b) A model for regulation of Wnt signalling by RSPO and its receptors based on our results and those by Hao et al.16 The schematic model takes into account the different binding sites of LGRs and ZNRF3/RNF43 on Rspos as determined by us and others25,26,27,28.