The Legionella Anti-autophagy Effector RavZ Targets the Autophagosome via PI3P-and Curvature-Sensing Motifs

被引：81

作者：

Horenkamp, Florian A. ^{[1
]}

Kauffman, Karlina J. ^{[1
]}

Kohler, Lara J. ^{[2
]}

Sherwood, Racquel K. ^{[2
]}

Krueger, Kathryn P. ^{[1
]}

Shteyn, Vladimir ^{[1
]}

Roy, Craig R. ^{[2
]}

Melia, Thomas J. ^{[1
]}

Reinisch, Karin M. ^{[1
]}

机构：

[1] Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06520 USA

[2] Yale Univ, Sch Med, Dept Microbial Pathogenesis, New Haven, CT 06520 USA

来源：

DEVELOPMENTAL CELL | 2015年 / 34卷 / 05期

关键词：

STRUCTURAL BASIS; SPECIFICITY; MACHINERY; SYSTEM;

D O I：

10.1016/j.devcel.2015.08.010

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Autophagy is a conserved membrane transport pathway used to destroy pathogenic microbes that access the cytosol of cells. The intracellular pathogen Legionella pneumophila interferes with autophagy by delivering an effector protein, RavZ, into the host cytosol. RavZ acts by cleaving membrane-conjugated Atg8/LC3 proteins from pre-autophagosomal structures. Its remarkable efficiency allows minute quantities of RavZ to block autophagy throughout the cell. To understand how RavZ targets pre-autophagosomes and specifically acts only on membrane-associated Atg8 proteins, we elucidated its structure. Revealed is a catalytic domain related in fold to Ulp family deubiquitinase-like enzymes and a C-terminal PI3P-binding module. RavZ targets the autophagosome via the PI3P-binding module and a catalytic domain helix, and it preferentially binds high-curvature membranes, intimating localization to highly curved domains in autophagosome intermediate membranes. RavZ-membrane interactions enhance substrate affinity, providing a mechanism for interfacial activation that also may be used by host autophagy proteins engaging only lipidated Atg8 proteins.

引用

页码：569 / 576

页数：8

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