5TJQ

Structure of WWP2 2,3-linker-HECT

5TJQ の概要

• エントリーDOI: 10.2210/pdb5tjq/pdb
• 関連するPDBエントリー: 5TJ7 5TJ8
• 分子名称: NEDD4-like E3 ubiquitin-protein ligase WWP2,NEDD4-like E3 ubiquitin-protein ligase WWP2 (2 entities in total)
• 機能のキーワード: wwp2, hect domain, ww2, wwp1, itch, autoinhibition, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus : O00308
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 53441.54

構造登録者

Chen, Z.,Gabelli, S.B. (登録日: 2016-10-04, 公開日: 2017-05-31, 最終更新日: 2024-11-20)

主引用文献

Chen, Z.,Jiang, H.,Xu, W.,Li, X.,Dempsey, D.R.,Zhang, X.,Devreotes, P.,Wolberger, C.,Amzel, L.M.,Gabelli, S.B.,Cole, P.A.
A Tunable Brake for HECT Ubiquitin Ligases.
Mol. Cell, 66:345-357.e6, 2017

PubMed Abstract: The HECT E3 ligases ubiquitinate numerous transcription factors and signaling molecules, and their activity must be tightly controlled to prevent cancer, immune disorders, and other diseases. In this study, we have found unexpectedly that peptide linkers tethering WW domains in several HECT family members are key regulatory elements of their catalytic activities. Biochemical, structural, and cellular analyses have revealed that the linkers can lock the HECT domain in an inactive conformation and block the proposed allosteric ubiquitin binding site. Such linker-mediated autoinhibition of the HECT domain can be relieved by linker post-translational modifications, but complete removal of the brake can induce hyperactive autoubiquitination and E3 self destruction. These results clarify the mechanisms of several HECT protein cancer associated mutations and provide a new framework for understanding how HECT ubiquitin ligases must be finely tuned to ensure normal cellular behavior.

PubMed: 28475870
DOI: 10.1016/j.molcel.2017.03.020

実験手法

X-RAY DIFFRACTION (2.75 Å)