Deubiquitination of phosphoribosyl-ubiquitin conjugates by phosphodiesterase-domain–containing Legionella effectors
| Autor: | Anil Akturk, Wendy H.J. Beck, Yuxin Mao, Marcus B. Smolka, Vitor M. Faça, Alan Sulpizio, Min Wan, Joseph P. Vogel, Michael Charles Lanz |
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| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Multidisciplinary biology Chemistry Effector Golgi apparatus biology.organism_classification Legionella pneumophila Deubiquitinating enzyme Cell biology Serine 03 medical and health sciences symbols.namesake 0302 clinical medicine Ubiquitin biology.protein symbols Gene 030217 neurology & neurosurgery 030304 developmental biology Deubiquitination |
| Zdroj: | Proceedings of the National Academy of Sciences. 116:23518-23526 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Posttranslational protein modification by ubiquitin (Ub) is a central eukaryotic mechanism that regulates a plethora of physiological processes. Recent studies unveiled an unconventional type of ubiquitination mediated by the SidE family of Legionella pneumophila effectors, such as SdeA, that catalyzes the conjugation of Ub to a serine residue of target proteins via a phosphoribosyl linker (hence named PR-ubiquitination). Comparable to the deubiquitinases in the canonical ubiquitination pathway, here we show that 2 paralogous Legionella effectors, Lpg2154 (DupA; deubiquitinase for PR-ubiquitination) and Lpg2509 (DupB), reverse PR-ubiquitination by specific removal of phosphoribosyl-Ub from substrates. Both DupA and DupB are fully capable of rescuing the Golgi fragmentation phenotype caused by exogenous expression of SdeA in mammalian cells. We further show that deletion of these 2 genes results in significant accumulation of PR-ubiquitinated species in host cells infected with Legionella In addition, we have identified a list of specific PR-ubiquitinated host targets and show that DupA and DupB play a role in modulating the association of PR-ubiquitinated host targets with Legionella-containing vacuoles. Together, our data establish a complete PR-ubiquitination and deubiquitination cycle and demonstrate the intricate control that Legionella has over this unusual Ub-dependent posttranslational modification. |
| Databáze: | OpenAIRE |
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