7YUI

Crystal structure of HOIL-1L(195-423) in complex with the linear tetra-ubiquitin

7YUI の概要

• エントリーDOI: 10.2210/pdb7yui/pdb
• 分子名称: Polyubiquitin-C, RanBP-type and C3HC4-type zinc finger-containing protein 1, ZINC ION, ... (4 entities in total)
• 機能のキーワード: e3, ubiquitination, protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 61724.88

構造登録者

Xiao, L.,Pan, L. (登録日: 2022-08-17, 公開日: 2023-08-30, 最終更新日: 2024-03-13)

主引用文献

Xu, X.,Wang, Y.,Zhang, Y.,Wang, Y.,Yin, Y.,Peng, C.,Gong, X.,Li, M.,Zhang, Y.,Zhang, M.,Tang, Y.,Zhou, X.,Liu, H.,Pan, L.
Mechanistic insights into the enzymatic activity of E3 ligase HOIL-1L and its regulation by the linear ubiquitin chain binding.
Sci Adv, 9:eadi4599-eadi4599, 2023

PubMed Abstract: Heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1L) serves as a unique E3 ligase to catalyze the mono-ubiquitination of relevant protein or sugar substrates and plays vital roles in numerous cellular processes in mammals. However, the molecular mechanism underpinning the E3 activity of HOIL-1L and the related regulatory mechanism remain elusive. Here, we report the crystal structure of the catalytic core region of HOIL-1L and unveil the key catalytic triad residues of HOIL-1L. Moreover, we discover that HOIL-1L contains two distinct linear di-ubiquitin binding sites that can synergistically bind to linear tetra-ubiquitin, and the binding of HOIL-1L with linear tetra-ubiquitin can promote its E3 activity. The determined HOIL-1L/linear tetra-ubiquitin complex structure not only elucidates the detailed binding mechanism of HOIL-1L with linear tetra-ubiquitin but also uncovers a unique allosteric ubiquitin-binding site for the activation of HOIL-1L. In all, our findings provide mechanistic insights into the E3 activity of HOIL-1L and its regulation by the linear ubiquitin chain binding.

PubMed: 37831767
DOI: 10.1126/sciadv.adi4599

実験手法

X-RAY DIFFRACTION (2.599 Å)