3O65

Crystal structure of a Josephin-ubiquitin complex: Evolutionary restraints on ataxin-3 deubiquitinating activity

3O65 の概要

• エントリーDOI: 10.2210/pdb3o65/pdb
• 分子名称: Putative ataxin-3-like protein, Ubiquitin, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: papain-like fold, ubiquitin thiolesterase, hydrolase-protein binding complex, hydrolase/protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus : Q9H3M9; Ubiquitin: Cytoplasm : P0CG47
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 123299.77

構造登録者

Weeks, S.D.,Grasty, K.C.,Hernandez-Cuebas, L.,Loll, P.J. (登録日: 2010-07-28, 公開日: 2010-11-24, 最終更新日: 2024-11-06)

主引用文献

Weeks, S.D.,Grasty, K.C.,Hernandez-Cuebas, L.,Loll, P.J.
Crystal Structure of a Josephin-Ubiquitin Complex: EVOLUTIONARY RESTRAINTS ON ATAXIN-3 DEUBIQUITINATING ACTIVITY.
J.Biol.Chem., 286:4555-4565, 2011

PubMed Abstract: The Josephin domain is a conserved cysteine protease domain found in four human deubiquitinating enzymes: ataxin-3, the ataxin-3-like protein (ATXN3L), Josephin-1, and Josephin-2. Josephin domains from these four proteins were purified and assayed for their ability to cleave ubiquitin substrates. Reaction rates differed markedly both among the different proteins and for different substrates with a given protein. The ATXN3L Josephin domain is a significantly more efficient enzyme than the ataxin-3 domain despite their sharing 85% sequence identity. To understand the structural basis of this difference, the 2.6 Å x-ray crystal structure of the ATXN3L Josephin domain in complex with ubiquitin was determined. Although ataxin-3 and ATXN3L adopt similar folds, they bind ubiquitin in different, overlapping sites. Mutations were made in ataxin-3 at selected positions, introducing the corresponding ATXN3L residue. Only three such mutations are sufficient to increase the catalytic activity of the ataxin-3 domain to levels comparable with that of ATXN3L, suggesting that ataxin-3 has been subject to evolutionary restraints that keep its deubiquitinating activity in check.

PubMed: 21118805
DOI: 10.1074/jbc.M110.177360

実験手法

X-RAY DIFFRACTION (2.7 Å)