Abstract
We have mapped a Jagged/Serrate-binding site to specific residues within the 12th EGF domain of human and Drosophila Notch. Two critical residues, involved in a hydrophobic interaction, provide a ligand-binding platform and are adjacent to a Fringe-sensitive residue that modulates Notch activity. Our data suggest that small variations within the binding site fine-tune ligand specificity, which may explain the observed sequence heterogeneity in mammalian Notch paralogues, and should allow the development of paralogue-specific ligand-blocking antibodies. As a proof of principle, we have generated a Notch-1-specific monoclonal antibody that blocks binding, thus paving the way for antibody tools for research and therapeutic applications.
DOI
10.1074/jbc.m112.428854
Publication Date
2013-03-01
Publication Title
Journal of Biological Chemistry
Volume
288
Issue
10
Publisher
Elsevier BV
ISSN
0021-9258
Embargo Period
2024-11-19
First Page
7305
Last Page
7312
Recommended Citation
Whiteman, P., de Madrid, B., Taylor, P., Li, D., & et al. (2013) 'Molecular Basis for Jagged-1/Serrate Ligand Recognition by the Notch Receptor', Journal of Biological Chemistry, 288(10), pp. 7305-7312. Elsevier BV: Available at: https://doi.org/10.1074/jbc.m112.428854
