NDLI: Molecular Basis for Jagged-1/Serrate Ligand Recognition by the Notch $Receptor^{*}$

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Molecular Basis for Jagged-1/Serrate Ligand Recognition by the Notch $Receptor^{*}$

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Viticheep, Nattnee Redfield, Christina Heslop, Rebecca Handford, Penny A. Li, Demin Tan, Joyce Zi Banham, Alison H. Whiteman, Pat Masiero, Massimo Lea, Susan M. Callaghan, Juliana Shimizu, Hideyuki Taylor, Paul Li, Ji Liang De Madrid, Beatriz Hernandez Harris, Adrian L. Baron, Martin
Description	Author Affiliation: Whiteman P ( Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom.)
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.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	10
Volume Number	288
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2013-03-08
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Calcium-Binding Proteins Metabolism Intercellular Signaling Peptides And Proteins Membrane Proteins Receptors, Notch Amino Acid Sequence Animals Antibodies, Monoclonal Immunology Pharmacology Blotting, Western Genetics Cell Line Cell Line, Tumor Drosophila Proteins Chemistry Flow Cytometry HEK293 Cells Ligands Mice Models, Molecular Molecular Sequence Data Mutation Protein Binding Drug Effects Protein Structure, Secondary Protein Structure, Tertiary Receptor, Notch1 Sequence Homology, Amino Acid Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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