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Science. 2012 Nov 23;338(6110):1072-6. doi: 10.1126/science.1227026. Epub 2012 Oct 25.

The Legionella effector RavZ inhibits host autophagy through irreversible Atg8 deconjugation.

Author information

1
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.

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.

PMID:
23112293
PMCID:
PMC3682818
DOI:
10.1126/science.1227026
[Indexed for MEDLINE]
Free PMC Article

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