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 language | English (US) |
|---|---|
| Article number | 4 |
| Journal | BMC Developmental Biology |
| Volume | 8 |
| DOIs | |
| State | Published - 2008 |
Fingerprint
ASJC Scopus subject areas
- Medicine(all)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Competition between Delta and the Abruptex domain of Notch
AU - Pei, Zifei
AU - Baker, Nicholas E.
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=40849083661&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=40849083661&partnerID=8YFLogxK
U2 - 10.1186/1471-213X-8-4
DO - 10.1186/1471-213X-8-4
M3 - Article
C2 - 18208612
AN - SCOPUS:40849083661
VL - 8
JO - BMC Developmental Biology
JF - BMC Developmental Biology
SN - 1471-213X
M1 - 4
ER -