5X0W

Molecular mechanism for the binding between Sharpin and HOIP

5X0W の概要

• エントリーDOI: 10.2210/pdb5x0w/pdb
• 分子名称: E3 ubiquitin-protein ligase RNF31, Sharpin (2 entities in total)
• 機能のキーワード: sharpin, hoip, linear ubiquitination, e3 enzyme, ligase-protein binding complex, ligase/protein binding
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm : Q96EP0; Cytoplasm, cytosol : Q9H0F6
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 120700.91

構造登録者

Liu, J.,Li, F.,Cheng, X.,Pan, L. (登録日: 2017-01-23, 公開日: 2017-10-18, 最終更新日: 2024-11-13)

主引用文献

Liu, J.,Wang, Y.,Gong, Y.,Fu, T.,Hu, S.,Zhou, Z.,Pan, L.
Structural Insights into SHARPIN-Mediated Activation of HOIP for the Linear Ubiquitin Chain Assembly
Cell Rep, 21:27-36, 2017

PubMed Abstract: The linear ubiquitin chain assembly complex (LUBAC) is the sole identified E3 ligase complex that catalyzes the formation of linear ubiquitin chain, and it is composed of HOIP, HOIL-1L, and SHARPIN. The E3 activity of HOIP can be effectively activated by HOIL-1L or SHARPIN, deficiency of which leads to severe immune system disorders. However, the underlying mechanism governing the HOIP-SHARPIN interaction and the SHARPIN-mediated activation of HOIP remains elusive. Here, we biochemically and structurally demonstrate that the UBL domain of SHARPIN specifically binds to the UBA domain of HOIP and thereby associates with and activates HOIP. We further uncover that SHARPIN and HOIL-1L can separately or synergistically bind to distinct sites of HOIP UBA with induced allosteric effects and thereby facilitate the E2 loading of HOIP for its activation. Thus, our findings provide mechanistic insights into the assembly and activation of LUBAC.

PubMed: 28978479
DOI: 10.1016/j.celrep.2017.09.031

実験手法

X-RAY DIFFRACTION (3 Å)