8IKT

Ternary trans-complex of phospho-parkin with cis ACT and pUb

8IKT の概要

• エントリーDOI: 10.2210/pdb8ikt/pdb
• 分子名称: E3 ubiquitin-protein ligase parkin, Ubiquitin, ZINC ION, ... (8 entities in total)
• 機能のキーワード: e3 ligase, ligase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 52313.22

構造登録者

Lenka, D.R.,Kumar, A. (登録日: 2023-03-01, 公開日: 2024-09-11, 最終更新日: 2024-09-18)

主引用文献

Lenka, D.R.,Dahe, S.V.,Antico, O.,Sahoo, P.,Prescott, A.R.,Muqit, M.M.K.,Kumar, A.
Additional feedforward mechanism of Parkin activation via binding of phospho-UBL and RING0 in trans.
Elife, 13:-, 2024

PubMed Abstract: Loss-of-function Parkin mutations lead to early-onset of Parkinson's disease. Parkin is an auto-inhibited ubiquitin E3 ligase activated by dual phosphorylation of its ubiquitin-like (Ubl) domain and ubiquitin by the PINK1 kinase. Herein, we demonstrate a competitive binding of the phospho-Ubl and RING2 domains towards the RING0 domain, which regulates Parkin activity. We show that phosphorylated Parkin can complex with native Parkin, leading to the activation of autoinhibited native Parkin in . Furthermore, we show that the activator element (ACT) of Parkin is required to maintain the enzyme kinetics, and the removal of ACT slows the enzyme catalysis. We also demonstrate that ACT can activate Parkin in but less efficiently than when present in the molecule. Furthermore, the crystal structure reveals a donor ubiquitin binding pocket in the linker connecting REP and RING2, which plays a crucial role in Parkin activity.

PubMed: 39221915
DOI: 10.7554/eLife.96699

実験手法

X-RAY DIFFRACTION (2.6 Å)