7UYG

Structure of the first OTU domain from Legionella pneumophila effector protein LotA

7UYG の概要

• エントリーDOI: 10.2210/pdb7uyg/pdb
• 分子名称: LotA, GLYCEROL, IODIDE ION, ... (4 entities in total)
• 機能のキーワード: deubiquitinase, otu, hydrolase
• 由来する生物種: Legionella pneumophila
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35109.93

構造登録者

Pruneda, J.N. (登録日: 2022-05-06, 公開日: 2022-12-21, 最終更新日: 2024-05-22)

主引用文献

Warren, G.D.,Kitao, T.,Franklin, T.G.,Nguyen, J.V.,Geurink, P.P.,Kubori, T.,Nagai, H.,Pruneda, J.N.
Mechanism of Lys6 poly-ubiquitin specificity by the L. pneumophila deubiquitinase LotA.
Mol.Cell, 83:105-120.e5, 2023

PubMed Abstract: The versatility of ubiquitination to control vast domains of eukaryotic biology is due, in part, to diversification through differently linked poly-ubiquitin chains. Deciphering signaling roles for some chain types, including those linked via K6, has been stymied by a lack of specificity among the implicated regulatory proteins. Forged through strong evolutionary pressures, pathogenic bacteria have evolved intricate mechanisms to regulate host ubiquitin during infection. Herein, we identify and characterize a deubiquitinase domain of the secreted effector LotA from Legionella pneumophila that specifically regulates K6-linked poly-ubiquitin. We demonstrate the utility of LotA for studying K6 poly-ubiquitin signals. We identify the structural basis of LotA activation and poly-ubiquitin specificity and describe an essential "adaptive" ubiquitin-binding domain. Without LotA activity during infection, the Legionella-containing vacuole becomes decorated with K6 poly-ubiquitin as well as the AAA ATPase VCP/p97/Cdc48. We propose that LotA's deubiquitinase activity guards Legionella-containing vacuole components from ubiquitin-dependent extraction.

PubMed: 36538933
DOI: 10.1016/j.molcel.2022.11.022

実験手法

X-RAY DIFFRACTION (1.5 Å)