title: Competition between Delta and the Abruptex domain of Notch.
abstract: 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.
  
  
  CONCLUSIONS
  The Abruptex region may serve as a barrier to Notch activation by competing for the ligand-binding domain of Notch.
authors.affiliation: Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. zpei@aecom.yu.edu
authors.forename: Zifei
authors.initials: Z
authors.lastname: Pei
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Baker
mesh_terms: D000818:Animals; D004331:Drosophila melanogaster / Q000378:metabolism*; D005643:Fucose / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011961:Receptors, Fc / Q000378:metabolism; D051880:Receptors, Notch / Q000737:chemistry* / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; D050505:Mutant Proteins; D011961:Receptors, Fc; D051880:Receptors, Notch; C064045:delta protein; D005643:Fucose