The Legionella effector RavZ inhibits host autophagy through irreversible Atg8 deconjugation

Augustine Choy, Julia Dancourt, Brian Mugo, Tamara J. O'Connor, Ralph R. Isberg, Thomas J. Melia, Craig R. Roy

Research output: Contribution to journalArticle

Abstract

Eukaryotic cells can use the autophagy pathway to defend against microbes that gain access to the cytosol or reside in pathogen-modified vacuoles. It remains unclear if pathogens have evolved specific mechanisms to manipulate autophagy. Here, we found that the intracellular pathogen Legionella pneumophila could interfere with autophagy by using the bacterial effector protein RavZ to directly uncouple Atg8 proteins attached to phosphatidylethanolamine on autophagosome membranes. RavZ hydrolyzed the amide bond between the carboxyl-terminal glycine residue and an adjacent aromatic residue in Atg8 proteins, producing an Atg8 protein that could not be reconjugated by Atg7 and Atg3. Thus, intracellular pathogens can inhibit autophagy by irreversibly inactivating Atg8 proteins during infection.

Original languageEnglish (US)
Pages (from-to)1072-1076
Number of pages5
JournalScience
Volume338
Issue number6110
DOIs
StatePublished - Nov 23 2012

ASJC Scopus subject areas

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    Choy, A., Dancourt, J., Mugo, B., O'Connor, T. J., Isberg, R. R., Melia, T. J., & Roy, C. R. (2012). The Legionella effector RavZ inhibits host autophagy through irreversible Atg8 deconjugation. Science, 338(6110), 1072-1076. https://doi.org/10.1126/science.1227026