2JQZ

Solution Structure of the C2 domain of human Smurf2

2JQZ の概要

• エントリーDOI: 10.2210/pdb2jqz/pdb
• 関連するPDBエントリー: 1zvd
• NMR情報: BMRB: 15306
• 分子名称: E3 ubiquitin-protein ligase SMURF2 (1 entity in total)
• 機能のキーワード: c2 domain, smurf2, ubiquitin protein ligase, phospholipid binding, ligase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14701.95

構造登録者

Wiesner, S.,Ogunjimi, A.A.,Wang, H.,Rotin, D.,Sicheri, F.,Wrana, J.L.,Forman-Kay, J.D. (登録日: 2007-06-15, 公開日: 2007-09-11, 最終更新日: 2024-05-08)

主引用文献

Wiesner, S.,Ogunjimi, A.A.,Wang, H.-R.,Rotin, D.,Sicheri, F.,Wrana, J.L.,Forman-Kay, J.D.
Autoinhibition of the HECT-Type Ubiquitin Ligase Smurf2 through Its C2 Domain
Cell(Cambridge,Mass.), 130:651-662, 2007

PubMed Abstract: Ubiquitination of proteins is an abundant modification that controls numerous cellular processes. Many Ubiquitin (Ub) protein ligases (E3s) target both their substrates and themselves for degradation. However, the mechanisms regulating their catalytic activity are largely unknown. The C2-WW-HECT-domain E3 Smurf2 downregulates transforming growth factor-beta (TGF-beta) signaling by targeting itself, the adaptor protein Smad7, and TGF-beta receptor kinases for degradation. Here, we demonstrate that an intramolecular interaction between the C2 and HECT domains inhibits Smurf2 activity, stabilizes Smurf2 levels in cells, and similarly inhibits certain other C2-WW-HECT-domain E3s. Using NMR analysis the C2 domain was shown to bind in the vicinity of the catalytic cysteine, where it interferes with Ub thioester formation. The HECT-binding domain of Smad7, which activates Smurf2, antagonizes this inhibitory interaction. Thus, interactions between C2 and HECT domains autoinhibit a subset of HECT-type E3s to protect them and their substrates from futile degradation in cells.

PubMed: 17719543
DOI: 10.1016/j.cell.2007.06.050

実験手法

SOLUTION NMR