2MPT

WW3 domain of Nedd4L in complex with its HECT domain PY motif

2MPT の概要

• エントリーDOI: 10.2210/pdb2mpt/pdb
• NMR情報: BMRB: 25000
• 分子名称: E3 ubiquitin-protein ligase NEDD4-like (2 entities in total)
• 機能のキーワード: ww, nedd4l, nedd4.2, hect, py, ww3, auto-ubiquitination, proteasomal degradation, ubiquitin ligase, ligase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm : Q96PU5 Q96PU5
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 7272.28

構造登録者

Escobedo, A.,Macias, M.J.,Gomes, T.,Aragon, E.,Martin-Malpartida, P.,Ruiz, L. (登録日: 2014-06-02, 公開日: 2014-10-22, 最終更新日: 2024-10-30)

主引用文献

Escobedo, A.,Gomes, T.,Aragon, E.,Martin-Malpartida, P.,Ruiz, L.,Macias, M.J.
Structural Basis of the Activation and Degradation Mechanisms of the E3 Ubiquitin Ligase Nedd4L.
Structure, 22:1446-1457, 2014

PubMed Abstract: We investigated the mechanisms of activation and degradation of the E3 ubiquitin ligase Nedd4L combining the available biochemical information with complementary biophysical techniques. Using nuclear magnetic resonance spectroscopy, we identified that the C2 domain binds Ca(2+) and inositol 1,4,5-trisphosphate (IP3) using the same interface that is used to interact with the HECT domain. Thus, we propose that the transition from the closed to the active form is regulated by a competition of IP3 and Ca(2+) with the HECT domain for binding to the C2 domain. We performed relaxation experiments and molecular dynamic simulations to determine the flexibility of the HECT structure and observed that its conserved PY motif can become solvent-exposed when the unfolding process is initiated. The structure of the WW3 domain bound to the HECT-PY site reveals the details of this interaction, suggesting a possible auto-ubquitination mechanism using two molecules, a partially unfolded one and a fully functional Nedd4L counterpart.

PubMed: 25295397
DOI: 10.1016/j.str.2014.08.016

実験手法

SOLUTION NMR