5C23

Parkin (S65DUblR0RBR)

5C23 の概要

• エントリーDOI: 10.2210/pdb5c23/pdb
• 分子名称: E3 ubiquitin-protein ligase parkin, ZINC ION, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: e3 ligase2, ligase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm, cytosol : O60260
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 93044.61

構造登録者

Kumar, A.,Aguirre, J.D.,Condos, T.E.C.,Martinez-Torres, R.J.,Chaugule, V.K.,Toth, R.,Sundaramoorthy, R.,Mercier, P.,Knebel, A.,Spratt, D.E.,Barber, K.R.,Shaw, G.S.,Walden, H. (登録日: 2015-06-15, 公開日: 2015-07-29, 最終更新日: 2024-01-10)

主引用文献

Kumar, A.,Aguirre, J.D.,Condos, T.E.,Martinez-Torres, R.J.,Chaugule, V.K.,Toth, R.,Sundaramoorthy, R.,Mercier, P.,Knebel, A.,Spratt, D.E.,Barber, K.R.,Shaw, G.S.,Walden, H.
Disruption of the autoinhibited state primes the E3 ligase parkin for activation and catalysis.
Embo J., 34:2506-2521, 2015

PubMed Abstract: The PARK2 gene is mutated in 50% of autosomal recessive juvenile parkinsonism (ARJP) cases. It encodes parkin, an E3 ubiquitin ligase of the RBR family. Parkin exists in an autoinhibited state that is activated by phosphorylation of its N-terminal ubiquitin-like (Ubl) domain and binding of phosphoubiquitin. We describe the 1.8 Å crystal structure of human parkin in its fully inhibited state and identify the key interfaces to maintain parkin inhibition. We identify the phosphoubiquitin-binding interface, provide a model for the phosphoubiquitin-parkin complex and show how phosphorylation of the Ubl domain primes parkin for optimal phosphoubiquitin binding. Furthermore, we demonstrate that the addition of phosphoubiquitin leads to displacement of the Ubl domain through loss of structure, unveiling a ubiquitin-binding site used by the E2~Ub conjugate, thus leading to active parkin. We find the role of the Ubl domain is to prevent parkin activity in the absence of the phosphorylation signals, and propose a model for parkin inhibition, optimization for phosphoubiquitin recruitment, release of inhibition by the Ubl domain and engagement with an E2~Ub conjugate. Taken together, this model provides a mechanistic framework for activating parkin.

PubMed: 26254304
DOI: 10.15252/embj.201592337

実験手法

X-RAY DIFFRACTION (2.37 Å)