2JMF

Solution structure of the Su(dx) WW4- Notch PY peptide complex

2JMF の概要

• エントリーDOI: 10.2210/pdb2jmf/pdb
• 関連するPDBエントリー: 1TK7
• NMR情報: BMRB: 15016
• 分子名称: E3 ubiquitin-protein ligase suppressor of deltex, Neurogenic locus Notch protein (2 entities in total)
• 機能のキーワード: ww domain, notch, nmr solution, complex, ligase-signaling protein complex, ligase/signaling protein
• 由来する生物種: Drosophila melanogaster (fruit fly); 詳細
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein. Processed neurogenic locus Notch protein: Nucleus: P07207
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 8089.98

構造登録者

Avis, J.M.,Blankley, R.T.,Jennings, M.D.,Golovanov, A.P. (登録日: 2006-11-05, 公開日: 2007-08-28, 最終更新日: 2023-12-20)

主引用文献

Jennings, M.D.,Blankley, R.T.,Baron, M.,Golovanov, A.P.,Avis, J.M.
Specificity and Autoregulation of Notch Binding by Tandem WW Domains in Suppressor of Deltex
J.Biol.Chem., 282:29032-29042, 2007

PubMed Abstract: WW domains target proline-tyrosine (PY) motifs and frequently function as tandem pairs. When studied in isolation, single WW domains are notably promiscuous and regulatory mechanisms are undoubtedly required to ensure selective interactions. Here, we show that the fourth WW domain (WW4) of Suppressor of Deltex, a modular Nedd4-like protein that down-regulates the Notch receptor, is the primary mediator of a direct interaction with a Notch-PY motif. A natural Trp to Phe substitution in WW4 reduces its affinity for general PY sequences and enhances selective interaction with the Notch-PY motif via compensatory specificity-determining interactions with PY-flanking residues. When WW4 is paired with WW3, domain-domain association, impeding proper folding, competes with Notch-PY binding to WW4. This novel mode of autoinhibition is relieved by binding of another ligand to WW3. Such cooperativity may facilitate the transient regulatory interactions observed in vivo between Su(dx) and Notch in the endocytic pathway. The highly conserved tandem arrangement of WW domains in Nedd4 proteins, and similar arrangements in more diverse proteins, suggests domain-domain communication may be integral to regulation of their associated cellular activities.

PubMed: 17656366
DOI: 10.1074/jbc.M703453200

実験手法

SOLUTION NMR