1YZB

Solution structure of the Josephin domain of Ataxin-3

1YZB の概要

• エントリーDOI: 10.2210/pdb1yzb/pdb
• NMR情報: BMRB: 6241
• 分子名称: Machado-Joseph disease protein 1 (1 entity in total)
• 機能のキーワード: papain-like fold, transcription
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus matrix: P54252
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 21053.77

構造登録者

Nicastro, G.,Masino, L.,Menon, R.P.,Knowles, P.P.,McDonald, N.Q.,Pastore, A. (登録日: 2005-02-28, 公開日: 2005-07-05, 最終更新日: 2024-05-29)

主引用文献

Nicastro, G.,Menon, R.P.,Masino, L.,Knowles, P.P.,McDonald, N.Q.,Pastore, A.
The solution structure of the Josephin domain of ataxin-3: Structural determinants for molecular recognition
Proc.Natl.Acad.Sci.Usa, 102:10493-10498, 2005

PubMed Abstract: The Josephin domain plays an important role in the cellular functions of ataxin-3, the protein responsible for the neurodegenerative Machado-Joseph disease. We have determined the solution structure of Josephin and shown that it belongs to the family of papain-like cysteine proteases, sharing the highest degree of structural similarity with bacterial staphopain. A currently unique structural feature of Josephin is a flexible helical hairpin formed by a 32-residue insertion, which could determine substrate specificity. By using the Josephin structure and the availability of NMR chemical shift assignments, we have mapped the enzyme active site by using the typical cysteine protease inhibitors, transepoxysuccinyl-L-eucylamido-4-guanidino-butane (E-64) and [L-3-trans-(propylcarbamyl)oxirane-2-carbonyl]-L-isoleucyl-L-proline (CA-074). We also demonstrate that the specific interaction of Josephin with the ubiquitin-like domain of the ubiquitin- and proteasome-binding factor HHR23B involves complementary exposed hydrophobic surfaces. The structural similarity with other deubiquitinating enzymes suggests a model for the proteolytic enzymatic activity of ataxin-3.

PubMed: 16020535
DOI: 10.1073/pnas.0501732102

実験手法

SOLUTION NMR