LGR4 distinguishes Norrin and RSPOs via distinct binding modes to drive separate Wnt signaling outcomes. Here, the authors use cryo-EM to reveal a LGR4–Norrin complex that blocks Frizzled4, highlighting a regulatory checkpoint and develop a nanobody that targets both ligands.
- Huarui Qiao
- Fangzheng Hu
- Yong Geng