Competition between Delta and the Abruptex domain of Notch

BMC Dev Biol. 2008 Jan 21;8:4. doi: 10.1186/1471-213X-8-4.


Background: Extracellular domains of the Notch family of signalling receptors contain many EGF repeat domains, as do their major ligands. Some EGF repeats are modified by O-fucosylation, and most have no identified role in ligand binding.

Results: Using a binding assay with purified proteins in vitro, it was determined that, in addition to binding to Delta, the ligand binding region of Notch bound to EGF repeats 22-27 of Notch, but not to other EGF repeat regions of Notch. EGF repeats 22-27 of Drosophila Notch overlap the genetically-defined 'Abruptex' region, and competed with Delta for binding to proteins containing the ligand-binding domain. Delta differed from the Abruptex domain in showing markedly enhanced binding at acid pH. Both Delta and the Abruptex region are heavily modified by protein O-fucosylation, but the split mutation of Drosophila Notch, which affects O-fucosylation of EGF repeat 14, did not affect binding of Notch to either Delta or the Abruptex region.

Conclusion: The Abruptex region may serve as a barrier to Notch activation by competing for the ligand-binding domain of Notch.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila melanogaster / metabolism*
  • Fucose / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Mutant Proteins / metabolism
  • Mutation / genetics
  • Protein Binding
  • Protein Structure, Tertiary
  • Receptors, Fc / metabolism
  • Receptors, Notch / chemistry*
  • Receptors, Notch / metabolism*
  • Repetitive Sequences, Amino Acid


  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Membrane Proteins
  • Mutant Proteins
  • Receptors, Fc
  • Receptors, Notch
  • delta protein
  • Fucose