Structural highlights
Function
[DTX_DROME] Regulator of Notch signaling, a signaling pathway involved in cell-cell communications that regulates a broad spectrum of cell-fate determinations. Mainly acts as a positive regulator of Notch, but it may also act as a negative regulator, depending on the developmental and cell context. Mediates the antineural activity of Notch. May function as a ubiquitin ligase protein in the Notch pathway.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Structure and Notch receptor binding of the tandem WWE domain of Deltex.,Zweifel ME, Leahy DJ, Barrick D Structure. 2005 Nov;13(11):1599-611. PMID:16271883[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Matsuno K, Diederich RJ, Go MJ, Blaumueller CM, Artavanis-Tsakonas S. Deltex acts as a positive regulator of Notch signaling through interactions with the Notch ankyrin repeats. Development. 1995 Aug;121(8):2633-44. PMID:7671825
- ↑ Ramain P, Khechumian K, Seugnet L, Arbogast N, Ackermann C, Heitzler P. Novel Notch alleles reveal a Deltex-dependent pathway repressing neural fate. Curr Biol. 2001 Nov 13;11(22):1729-38. PMID:11719214
- ↑ Matsuno K, Ito M, Hori K, Miyashita F, Suzuki S, Kishi N, Artavanis-Tsakonas S, Okano H. Involvement of a proline-rich motif and RING-H2 finger of Deltex in the regulation of Notch signaling. Development. 2002 Feb;129(4):1049-59. PMID:11861487
- ↑ Zweifel ME, Leahy DJ, Barrick D. Structure and Notch receptor binding of the tandem WWE domain of Deltex. Structure. 2005 Nov;13(11):1599-611. PMID:16271883 doi:10.1016/j.str.2005.07.015
