7W54

Crystal structure of a bacterial OTU DUB with Ub-PA

7W54 の概要

• エントリーDOI: 10.2210/pdb7w54/pdb
• 分子名称: Lpg2248, Polyubiquitin-B, prop-2-en-1-amine, ... (4 entities in total)
• 機能のキーワード: dub, hydrolase
• 由来する生物種: Legionella pneumophila subsp. pneumophila str. Philadelphia 1; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 154528.35

構造登録者

Zhen, X.,Ouyang, S.Y. (登録日: 2021-11-29, 公開日: 2022-08-24, 最終更新日: 2023-04-05)

主引用文献

Luo, J.,Ruan, X.,Huang, Z.,Li, Z.,Ye, L.,Wu, Y.,Zhen, X.,Ouyang, S.
Structural basis for the dual catalytic activity of the Legionella pneumophila ovarian tumor (OTU) domain deubiquitinase LotA.
J.Biol.Chem., 298:102414-102414, 2022

PubMed Abstract: Legionella pneumophila, a bacterial pathogen that causes a severe pneumonia known as Legionnaires' disease, extensively exploits the ubiquitin (Ub) pathway in the infected host cells through certain virulence effectors excreted by the Dot/Icm system. To date, several Dot/Icm effectors have been found to act as Ub ligases, and four effectors, including LotA, LotB, LotC, and Ceg7, have been identified as deubiquitinases (DUBs) from the ovarian tumor (OTU) domain family. LotA is unique among other OTU DUBs because it possesses two distinct DUB domains and exclusively exhibits catalytic activity against K6-linked diUb and polyUb chains. However, the structure of LotA and the molecular mechanism for the dual DUB activity remains elusive. In this study, we solved the structure of LotA in complex with proximally bound Ub and distal covalently bound Ub. Both Ub molecules are bound to the DUB1 domain and mimic a K6-linked diUb. Structural analysis reveals that the DUB1 domain utilizes a distinct mechanism for recognition of the K6-linked diUb within a large S1' binding site that is uncommon to OTU DUBs. Structural fold of the LotA DUB2 domain closely resembles LotB and LotC, similarly containing an extra α-helix lobe that has been demonstrated to play an important role in Ub binding. Collectively, our study uncovers the structural basis for the dual catalytic activity of the unique OTU family DUB LotA.

PubMed: 36007613
DOI: 10.1016/j.jbc.2022.102414

実験手法

X-RAY DIFFRACTION (2.64 Å)