title: The Legionella effector RavZ inhibits host autophagy through irreversible Atg8 deconjugation.
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.
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Augustine
authors.initials: A
authors.lastname: Choy
authors.forename: Julia
authors.initials: J
authors.lastname: Dancourt
authors.forename: Brian
authors.initials: B
authors.lastname: Mugo
authors.forename: Tamara J
authors.initials: TJ
authors.lastname: O'Connor
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Isberg
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Melia
authors.forename: Craig R
authors.initials: CR
authors.lastname: Roy
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001343:Autophagy; D000071193:Autophagy-Related Protein 7; D000071190:Autophagy-Related Protein 8 Family; D000071183:Autophagy-Related Proteins; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018929:Cell Culture Techniques; D057056:Cysteine Proteases / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D005998:Glycine / Q000378:metabolism; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D006868:Hydrolysis; D016952:Legionella pneumophila / Q000201:enzymology* / Q000235:genetics; D007877:Legionnaires' Disease / Q000378:metabolism* / Q000382:microbiology; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism / Q000382:microbiology; D044764:Ubiquitin-Activating Enzymes / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000071190:Autophagy-Related Protein 8 Family; D000071183:Autophagy-Related Proteins; D001426:Bacterial Proteins; C498698:GABARAPL2 protein, human; D008840:Microfilament Proteins; D044763:Ubiquitin-Conjugating Enzymes; D057056:Cysteine Proteases; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes; C455621:ATG3 protein, human; D005998:Glycine