Fig. 2: Binding interface between LGR4 and Norrin.
From: Distinct structural mechanisms of LGR4 modulation by Norrin and RSPOs in Wnt/β-catenin signaling
a The binding interface between the LGR4 ectodomain and Norrin in the LGR4-Norrin complex, LGR4 transmembrane is omitted for clarity, LGR4 is shown in light green, while Norrin is depicted in violet and orange. b Detailed view of the specific interactions between LGR4 (light green) and Norrin (violet), highlighting key binding residues. c The LGR4 double mutant (H207N/H209T) was transiently expressed in LGR4-knockout HEK293T/17 cells and stimulated with 100 nM Norrin-Fc. Wnt/β-catenin signaling activity was assessed using the TOPFlash luciferase reporter assay. The H207N/H209T mutation significantly impaired Norrin-induced signaling compared to wild-type LGR4, n = 3, p < 0.001 (***). Error bars represent the S.E.M. Source data are provided as a Source Data file. d Superimposed structures of the LGR4-Norrin and FZD4 CRD-Norrin complexes (PDB code: 5CL1), aligned based on the Norrin dimer. This alignment reveals a steric clash between FZD4 CRD and LGR4 when both attempt to bind Norrin. For clarity, transmembrane regions of LGR4 are omitted. LGR4 is colored light green and cyan, Norrin in violet and orange, and FZD4 CRD in pink. e Table summarizing Norrin binding residues, their variants, and associated disease implications with the LGR4 and FZD4 receptors57,66,67,68,69.
