5Y3T

Crystal structure of hetero-trimeric core of LUBAC: HOIP double-UBA complexed with HOIL-1L UBL and SHARPIN UBL

5Y3T の概要

• エントリーDOI: 10.2210/pdb5y3t/pdb
• 分子名称: RanBP-type and C3HC4-type zinc finger-containing protein 1, E3 ubiquitin-protein ligase RNF31, Sharpin, ... (5 entities in total)
• 機能のキーワード: hoip, hoil-1l, sharpin, linear-ubiquitin assembly complex, nf-kb activation, lubac tethering motif, lubac stabilization, ligase
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 53771.72

構造登録者

Tokunaga, A.,Fujita, H.,Ariyoshi, M.,Ohki, I.,Tochio, H.,Iwai, K.,Shirakawa, M. (登録日: 2017-07-31, 公開日: 2018-05-02, 最終更新日: 2023-11-22)

主引用文献

Fujita, H.,Tokunaga, A.,Shimizu, S.,Whiting, A.L.,Aguilar-Alonso, F.,Takagi, K.,Walinda, E.,Sasaki, Y.,Shimokawa, T.,Mizushima, T.,Ohki, I.,Ariyoshi, M.,Tochio, H.,Bernal, F.,Shirakawa, M.,Iwai, K.
Cooperative Domain Formation by Homologous Motifs in HOIL-1L and SHARPIN Plays A Crucial Role in LUBAC Stabilization.
Cell Rep, 23:1192-1204, 2018

PubMed Abstract: The linear ubiquitin chain assembly complex (LUBAC) participates in inflammatory and oncogenic signaling by conjugating linear ubiquitin chains to target proteins. LUBAC consists of the catalytic HOIP subunit and two accessory subunits, HOIL-1L and SHARPIN. Interactions between the ubiquitin-associated (UBA) domains of HOIP and the ubiquitin-like (UBL) domains of two accessory subunits are involved in LUBAC stabilization, but the precise molecular mechanisms underlying the formation of stable trimeric LUBAC remain elusive. We solved the co-crystal structure of the binding regions of the trimeric LUBAC complex and found that LUBAC-tethering motifs (LTMs) located N terminally to the UBL domains of HOIL-1L and SHARPIN heterodimerize and fold into a single globular domain. This interaction is resistant to dissociation and plays a critical role in stabilizing trimeric LUBAC. Inhibition of LTM-mediated HOIL-1L/SHARPIN dimerization profoundly attenuated the function of LUBAC, suggesting LTM as a superior target of LUBAC destabilization for anticancer therapeutics.

PubMed: 29694895
DOI: 10.1016/j.celrep.2018.03.112

実験手法

X-RAY DIFFRACTION (2.4 Å)