Structural features of the Notch ankyrin domain-Deltex WWE₂ domain heterodimer determined by NMR spectroscopy and functional implications.

ABSTRACT: The Notch signaling pathway, an important cell fate determination pathway, is modulated by the ubiquitin ligase Deltex. Here, we investigate the structural basis for Deltex-Notch interaction. We used nuclear magnetic resonance (NMR) spectroscopy to assign the backbone of the Drosophila Deltex WWE₂ domain and mapped the binding site of the Notch ankyrin (ANK) domain to the N-terminal WWE_A motif. Using cultured Drosophila S2R+ cells, we find that point substitutions within the ANK-binding surface of Deltex disrupt Deltex-mediated enhancement of Notch transcriptional activation and disrupt ANK binding in cells and in vitro. Likewise, ANK substitutions that disrupt Notch-Deltex heterodimer formation in vitro block disrupt Deltex-mediated stimulation of Notch transcription

SUBMITTER: Carter AA 

PROVIDER: S-EPMC10338078 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature