2A90

Structure and Notch Receptor Binding of the Tandem WWE Domain of Deltex.

(2005) Structure 13: 1599-1611

• PubMed: 16271883 Search on PubMed
• DOI: https://doi.org/10.1016/j.str.2005.07.015
• Primary Citation of Related Structures:  
  2A90


• PubMed Abstract: 
  

  Deltex is a cytosolic effector of Notch signaling thought to bind through its N-terminal domain to the Notch receptor. Here we report the structure of the Drosophila Deltex N-terminal domain, which contains two tandem WWE sequence repeats. The WWE repeats, which adopt a novel fold, are related by an approximate two-fold axis of rotation. Although the WWE repeats are structurally distinct, they interact extensively and form a deep cleft at their junction that appears well suited for ligand binding. The two repeats are thermodynamically coupled; this coupling is mediated in part by a conserved segment that is immediately C-terminal to the second WWE domain. We demonstrate that although the Deltex WWE tandem is monomeric in solution, it forms a heterodimer with the ankyrin domain of the Notch receptor. These results provide structural and functional insight into how Deltex modulates Notch signaling, and how WWE modules recognize targets for ubiquitination.

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Organizational Affiliation: 

T.C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, Maryland 21218, USA.