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.
Original language | English (US) |
---|---|
Pages (from-to) | 105-120.e5 |
Journal | Molecular Cell |
Volume | 83 |
Issue number | 1 |
DOIs | |
State | Published - Jan 5 2023 |
Keywords
- Legionella pneumophila
- VCP/p97/Cdc48
- bacterial effector
- deubiquitinase
- ubiquitin
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology