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The soluble ligand Y box-1 activates Notch3 receptor by binding to epidermal growth factor like repeats 20-23

Gera, S and Dighe, RR (2018) The soluble ligand Y box-1 activates Notch3 receptor by binding to epidermal growth factor like repeats 20-23. In: Archives of Biochemistry and Biophysics, 660 . pp. 129-136.

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Official URL: https://org.doi/10.1016/j.abb.2018.10.009


The transduction of signal by the Notch receptors to the intracellular domain is highly regulated and relies on binding of the ligands to the Epidermal growth factor Like Repeats (ELRs) of receptor's extracellular domain. Both canonical and non-canonical ligands are known to interact with different ELRs and activate Notch receptors. The aim of this study was to investigate the interaction of a soluble non-canonical ligand, Y box-1 (Yb-1) with Notch3 receptor ELRs. Polyclonal antibodies were employed as novel tools to identify the binding site of this ligand. Using various ligand binding and signaling assays, soluble Yb-1 was found to interact specifically with the Notch3 receptor, but not with Notch1. The ELRs 17–24 of Notch3 were identified as the binding site for Yb-1. Further, Yb-1 and Notch3 ELRs 17–24 structures were modelled and the Yb-1-Notch3 interaction interface was predicted to be Notch3 ELRs 20–23. Binding of the Yb-1 with Notch3 ELRs different from those reported for canonical DSL ligands also transduced the signal to the intracellular domain through the negative regulatory region. In conclusion, study highlights the importance of molecular modifications in different Notch3 ELRs for the transduction of signal to the negative regulatory region.

Item Type: Journal Article
Publication: Archives of Biochemistry and Biophysics
Publisher: Academic Press Inc.
Additional Information: The copyright for this article belongs to Academic Press Inc.
Keywords: epidermal growth factor derivative; epidermal growth factor like repeats 17-24; epidermal growth factor like repeats 20-23; Notch3 receptor; unclassified drug; Y box binding protein 1; epidermal growth factor; JAG1 protein, human; ligand; Notch3 receptor; protein binding; protein Jagged 1; Y box binding protein 1; YBX1 protein, human, Article; conformational transition; HEK293 cell line; human; human cell; ligand binding; Notch signaling; priority journal; protein expression; amino acid repeat; animal; chemistry; CHO cell line; Cricetulus; metabolism; protein domain; signal transduction; solubility, Animals; CHO Cells; Cricetulus; Epidermal Growth Factor; Jagged-1 Protein; Ligands; Protein Binding; Protein Domains; Receptor, Notch3; Repetitive Sequences, Amino Acid; Signal Transduction; Solubility; Y-Box-Binding Protein 1
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited: 29 Jul 2022 11:48
Last Modified: 29 Jul 2022 11:48
URI: https://eprints.iisc.ac.in/id/eprint/75053

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