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Updated: Oct 27, 2025
05:48
Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
Published on: January 2, 2018
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Notch-Jagged signaling complex defined by an interaction mosaic.
Matthieu R Zeronian1, Oleg Klykov2,3,4, Júlia Portell I de Montserrat1
1Structural Biochemistry, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands.
Summary
The Notch signaling pathway
Area of Science:
- Cellular biology
- Biochemistry
- Structural biology
Background:
- The Notch signaling pathway is crucial for cell-fate determination, but its activation mechanism by the Jagged1 ligand is not fully understood.
- Dysregulation of Notch signaling is linked to developmental disorders and cancer.
Purpose of the Study:
- To elucidate the molecular interactions between the Notch1 receptor and Jagged1 ligand that activate Notch signaling.
- To identify the specific regions and interaction network governing Notch1-Jagged1 engagement.
Main Methods:
- Cross-linking mass spectrometry (XL-MS)
- Biophysical techniques
- Structural analysis
- Small-angle X-ray scattering (SAXS)
Main Results:
- Identified a five-region interaction network between Notch1 and Jagged1, involving specific EGF domains and a cysteine-rich domain.
- Demonstrated intramolecular interactions within Jagged1's binding sites.
- Revealed nonlinear architectures of the Notch1-Jagged1 complex, indicating direct engagement of critical regions.
Conclusions:
- The Notch1-Jagged1 activation mechanism involves direct engagement of specific, non-distal regions, redefining current understanding.
- These findings offer insights into therapeutic strategies targeting Notch signaling dysregulation.
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