The Legionella Effector RavZ Inhibits Host Autophagy Through Irreversible Atg8 Deconjugation

被引:363
作者
Choy, Augustine [2 ]
Dancourt, Julia [1 ]
Mugo, Brian [1 ]
O'Connor, Tamara J. [3 ,4 ]
Isberg, Ralph R. [3 ,4 ]
Melia, Thomas J. [1 ]
Roy, Craig R. [2 ]
机构
[1] Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06510 USA
[2] Yale Univ, Sch Med, Dept Microbial Pathogenesis, New Haven, CT USA
[3] Tufts Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02111 USA
[4] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA
关键词
PNEUMOPHILA GENOME; SYSTEM; PATHWAY;
D O I
10.1126/science.1227026
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1072 / 1076
页数:5
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