3BY4

Structure of Ovarian Tumor (OTU) domain in complex with Ubiquitin

3BY4 の概要

• エントリーDOI: 10.2210/pdb3by4/pdb
• 関連するPDBエントリー: 3C0R
• 分子名称: Ubiquitin thioesterase OTU1, Ubiquitin, 3-AMINOPROPANE, ... (4 entities in total)
• 機能のキーワード: ubiquitin hydrolase, deubiquitinase, cell cycle, hydrolase
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast); 詳細
• 細胞内の位置: Cytoplasm : P43558
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 32447.92

構造登録者

Messick, T.E.,Marmorstein, R. (登録日: 2008-01-15, 公開日: 2008-02-19, 最終更新日: 2025-03-26)

主引用文献

Messick, T.E.,Russell, N.S.,Iwata, A.J.,Sarachan, K.L.,Shiekhattar, R.,Shanks, J.R.,Reyes-Turcu, F.E.,Wilkinson, K.D.,Marmorstein, R.
Structural basis for ubiquitin recognition by the Otu1 ovarian tumor domain protein
J.Biol.Chem., 283:11038-11049, 2008

PubMed Abstract: Ubiquitination of proteins modifies protein function by either altering their activities, promoting their degradation, or altering their subcellular localization. Deubiquitinating enzymes are proteases that reverse this ubiquitination. Previous studies demonstrate that proteins that contain an ovarian tumor (OTU) domain possess deubiquitinating activity. This domain of approximately 130 amino acids is weakly similar to the papain family of proteases and is highly conserved from yeast to mammals. Here we report structural and functional studies on the OTU domain-containing protein from yeast, Otu1. We show that Otu1 binds polyubiquitin chain analogs more tightly than monoubiquitin and preferentially hydrolyzes longer polyubiquitin chains with Lys(48) linkages, having little or no activity on Lys(63)- and Lys(29)-linked chains. We also show that Otu1 interacts with Cdc48, a regulator of the ER-associated degradation pathway. We also report the x-ray crystal structure of the OTU domain of Otu1 covalently complexed with ubiquitin and carry out structure-guided mutagenesis revealing a novel mode of ubiquitin recognition and a variation on the papain protease catalytic site configuration that appears to be conserved within the OTU family of ubiquitin hydrolases. Together, these studies provide new insights into ubiquitin binding and hydrolysis by yeast Otu1 and other OTU domain-containing proteins.

PubMed: 18270205
DOI: 10.1074/jbc.M704398200

実験手法

X-RAY DIFFRACTION (1.55 Å)