A conserved face of the Jagged/Serrate DSL domain is involved in Notch trans-activation and cis-inhibition

Jemima Cordle, Steven Johnson, Joyce Zi Yan Tay, Pietro Roversi, Marian B. Wilkin, Beatriz Hernández De Madrid, Hideyuki Shimizu, Sacha Jensen, Pat Whiteman, Boquan Jin, Christina Redfield, Martin Baron, Susan M. Lea, Penny A. Handford

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The Notch receptor and its ligands are key components in a core metazoan signaling pathway that regulates the spatial patterning, timing and outcome of many cell-fate decisions. Ligands contain a disulfide-rich Delta/Serrate/LAG-2 (DSL) domain required for Notch trans-activation or cis-inhibition. Here we report the X-ray structure of a receptor binding region of a Notch ligand, the DSL-EGF3 domains of human Jagged-1 (J-1DSL-EGF3). The structure reveals a highly conserved face of the DSL domain, and we show, by functional analysis of Drosophila melanogster ligand mutants, that this surface is required for both cis- and trans-regulatory interactions with Notch. We also identify, using NMR, a surface of Notch-1 involved in J-1DSL-EGF3 binding. Our data imply that cis- and trans-regulation may occur through the formation of structurally distinct complexes that, unexpectedly, involve the same surfaces on both ligand and receptor. © 2008 Nature Publishing Group.
    Original languageEnglish
    Pages (from-to)849-857
    Number of pages8
    JournalNature Structural and Molecular Biology
    Volume15
    Issue number8
    DOIs
    Publication statusPublished - Aug 2008

    Fingerprint

    Dive into the research topics of 'A conserved face of the Jagged/Serrate DSL domain is involved in Notch trans-activation and cis-inhibition'. Together they form a unique fingerprint.

    Cite this