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7 septembre 2018: 1 événement

  • Département Biologie des Génomes

    Vendredi 7 septembre 11:00-12:00 - Rami Hannoush - Department of Early Discovery Biochemistry, Genentech Inc, CA USA

    Pharmacological modulation of Wnt signaling in intestinal stem cells

    Résumé : The Frizzled (FZD) 7 receptor (FZD7) is enriched in LGR5+ intestinal stem cells and plays a critical role in their self-renewal. In general, FZD proteins interact with Wnt signaling proteins via, in part, a lipid-binding groove on the extracellular cysteine-rich domain (CRD) of the FZD receptor. This presentation will highlight our lab’s recent efforts in providing new structural insights into the molecular arrangement of members of the FZD receptor family and their mode of regulation by cis-unsaturated fatty acids. We also highlight drug discovery approaches and structural bases for targeting specific FZD isoforms. In particular, we describe the identification of a potent peptide that selectively binds to the FZD7 CRD at a previously uncharacterized site and alters the conformation of the CRD and the architecture of its lipid-binding groove. Treatment with the FZD7-binding peptide impaired Wnt signaling in cultured cells and stem cell function in intestinal organoids.
    Contact : GIGLIONE Carmela <carmela.giglione i2bc.paris-saclay.fr>

    Lieu : Bibliothèque - bâtiment 34 - Campus CNRS de Gif-sur-Yvette

    En savoir plus : Département Biologie des Génomes