RRC ID 30213
著者 Choy A, Dancourt J, Mugo B, O'Connor TJ, Isberg RR, Melia TJ, Roy CR.
タイトル The Legionella effector RavZ inhibits host autophagy through irreversible Atg8 deconjugation.
ジャーナル Science
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.
巻・号 338(6110)
ページ 1072-6
公開日 2012-11-23
DOI 10.1126/science.1227026
PII science.1227026
PMID 23112293
PMC PMC3682818
MeSH Adaptor Proteins, Signal Transducing / antagonists & inhibitors* Adaptor Proteins, Signal Transducing / metabolism Autophagy* Autophagy-Related Protein 7 Autophagy-Related Protein 8 Family Autophagy-Related Proteins Bacterial Proteins / genetics Bacterial Proteins / metabolism* Cell Culture Techniques Cysteine Proteases / genetics Cysteine Proteases / metabolism* Gene Deletion Glycine / metabolism HEK293 Cells Host-Pathogen Interactions* Humans Hydrolysis Legionella pneumophila / enzymology* Legionella pneumophila / genetics Legionnaires' Disease / metabolism* Legionnaires' Disease / microbiology Microfilament Proteins / antagonists & inhibitors* Microfilament Proteins / metabolism Phagosomes / metabolism Phagosomes / microbiology Ubiquitin-Activating Enzymes / metabolism Ubiquitin-Conjugating Enzymes / metabolism
IF 41.846
引用数 233
WOS 分野 CELL BIOLOGY
リソース情報
実験動物マウス RBRC00806