Competition between Delta and the Abruptex domain of Notch

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

Original languageEnglish (US)
Article number4
JournalBMC Developmental Biology
Volume8
DOIs
StatePublished - 2008

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Epidermal Growth Factor
Ligands
Drosophila
Carrier Proteins
Proteins
Mutation
Acids

ASJC Scopus subject areas

  • Medicine(all)

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Competition between Delta and the Abruptex domain of Notch. / Pei, Zifei; Baker, Nicholas E.

In: BMC Developmental Biology, Vol. 8, 4, 2008.

Research output: Contribution to journalArticle

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