NELL2-Robo3 complex structure reveals mechanisms of receptor activation for axon guidance

Abstract

Robo3 is a divergent, multifunctional member of the Robo receptor family that mediates axon guidance by its ligand NELL2 instead of the canonical Slit ligands. Here, the authors present the crystal structures of human Robo3 in complex with NELL1 and NELL2, and they show through biophysical and functional assays how NELL-Robo3 affinity and ligand-induced receptor multimerization control axon guidance activity.