2AGA

De-ubiquitinating function of ataxin-3: insights from the solution structure of the Josephin domain

2AGA の概要

• エントリーDOI: 10.2210/pdb2aga/pdb
• NMR情報: BMRB: 6742
• 分子名称: Machado-Joseph disease protein 1 (1 entity in total)
• 機能のキーワード: polyglutamine, ubiquitin, uim, ataxia, vcp/p97, transcription
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 21820.61

構造登録者

Mao, Y.,Senic-Matuglia, F.,Di Fiore, P.,Polo, S.,Hodsdon, M.E.,De Camilli, P. (登録日: 2005-07-26, 公開日: 2005-08-30, 最終更新日: 2024-05-08)

主引用文献

Mao, Y.,Senic-Matuglia, F.,Di Fiore, P.P.,Polo, S.,Hodsdon, M.E.,De Camilli, P.
Deubiquitinating function of ataxin-3: insights from the solution structure of the Josephin domain.
Proc.Natl.Acad.Sci.Usa, 102:12700-12705, 2005

PubMed Abstract: Spinocerebellar ataxia type 3 is a human neurodegenerative disease resulting from polyglutamine tract expansion. The affected protein, ataxin-3, which contains an N-terminal Josephin domain followed by tandem ubiquitin (Ub)-interacting motifs (UIMs) and a polyglutamine stretch, has been implicated in the function of the Ub proteasome system. NMR-based structural analysis has now revealed that the Josephin domain binds Ub and has a papain-like fold that is reminiscent of that of other deubiquitinases, despite primary sequence divergence but consistent with its deubiqutinating activity. Mutation of the catalytic Cys enhances the stability of a complex between ataxin-3 and polyubiquitinated proteins. This effect depends on the integrity of the UIM region, suggesting that the UIMs are bound to the substrate polyubiquitin during catalysis. We propose that ataxin-3 functions as a polyubiquitin chain-editing enzyme.

PubMed: 16118278
DOI: 10.1073/pnas.0506344102

実験手法

SOLUTION NMR