Ligand Interactions Notch signaling pathway

crystal structure of notch1-dll4 complex depicted interaction predicted occur between 2 cells (pdb id: 4xlw)

notch signaling initiated when notch receptors on cell surface engage ligands presented in trans on opposing cells. despite expansive size of notch extracellular domain, has been demonstrated egf domains 11 , 12 critical determinants interactions delta. additional studies have implicated regions outside of notch egf11-12 in ligand binding. example, notch egf domain 8 plays role in selective recognition of serrate/jagged , egf domains 6-15 required maximal signaling upon ligand stimulation. crystal structure of interacting regions of notch1 , delta-like 4 (dll4) provided molecular-level visualization of notch-ligand interactions, , revealed n-terminal mnnl (or c2) , dsl domains of ligands bind notch egf domains 12 , 11, respectively. notch1-dll4 structure illuminated direct role notch o-linked fucose , glucose moieties in ligand recognition, , rationalized structural mechanism glycan-mediated tuning of notch signaling.