5N2W

WT-Parkin and pUB complex

5N2W の概要

• エントリーDOI: 10.2210/pdb5n2w/pdb
• 分子名称: E3 ubiquitin-protein ligase parkin,E3 ubiquitin-protein ligase parkin, Polyubiquitin-B, ZINC ION, ... (6 entities in total)
• 機能のキーワード: complex structure of parkin and pub, transferase, ligase
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm, cytosol : O60260; Ubiquitin: Cytoplasm : P0CG47
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 54949.82

構造登録者

Kumar, A.,Chaugule, V.K.,Johnson, C.,Toth, R.,Sundaramoorthy, R.,Knebel, A.,Walden, H. (登録日: 2017-02-08, 公開日: 2017-04-19, 最終更新日: 2024-11-13)

主引用文献

Kumar, A.,Chaugule, V.K.,Condos, T.E.C.,Barber, K.R.,Johnson, C.,Toth, R.,Sundaramoorthy, R.,Knebel, A.,Shaw, G.S.,Walden, H.
Parkin-phosphoubiquitin complex reveals cryptic ubiquitin-binding site required for RBR ligase activity.
Nat. Struct. Mol. Biol., 24:475-483, 2017

PubMed Abstract: RING-between-RING (RBR) E3 ligases are a class of ubiquitin ligases distinct from RING or HECT E3 ligases. An important RBR ligase is Parkin, mutations in which lead to early-onset hereditary Parkinsonism. Parkin and other RBR ligases share a catalytic RBR module but are usually autoinhibited and activated via distinct mechanisms. Recent insights into Parkin regulation predict large, unknown conformational changes during Parkin activation. However, current data on active RBR ligases reflect the absence of regulatory domains. Therefore, it remains unclear how individual RBR ligases are activated, and whether they share a common mechanism. We now report the crystal structure of a human Parkin-phosphoubiquitin complex, which shows that phosphoubiquitin binding induces movement in the 'in-between RING' (IBR) domain to reveal a cryptic ubiquitin-binding site. Mutation of this site negatively affects Parkin's activity. Furthermore, ubiquitin binding promotes cooperation between Parkin molecules, which suggests a role for interdomain association in the RBR ligase mechanism.

PubMed: 28414322
DOI: 10.1038/nsmb.3400

実験手法

X-RAY DIFFRACTION (2.68 Å)