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

Journal Article · Sat Jan 01 04:00:00 EST 2005 · Structure

DOI:https://doi.org/10.1016/j.str.2005.07.015· OSTI ID:913713

Zweifel, M; Leahy, D; Barrick, D

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.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 913713
• Report Number(s): BNL--78281-2007-JA
• Journal Information: Structure, Journal Name: Structure Vol. 13
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
BIOLOGICAL FUNCTIONS
DROSOPHILA
LIGANDS
MORPHOLOGY
national synchrotron light source