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Molecular Basis for Jagged-1/Serrate Ligand Recognition by the Notch Receptor*

Journal article published in 2013 by Pat Whiteman, Beatriz Hernandez de Madrid, Paul Taylor, Demin Li, Rebecca Heslop, Nattnee Viticheep, Joyce Zi Tan, Hideyuki Shimizu, Juliana Callaghan, Massimo Masiero, Ji Liang Li, Alison H. Banham ORCID, Adrian L. Harris, Susan M. Lea, Christina Redfield and other authors.
This paper is available in a repository.
This paper is available in a repository.

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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 which 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.