The Legionella Anti-autophagy Effector RavZ Targets the Autophagosome via PI3P- and Curvature-Sensing Motifs.
The Legionella Anti-autophagy Effector RavZ Targets the Autophagosome via PI3P- and Curvature-Sensing Motifs.
复制标题
军团菌的抗噬效应效果RAVZ通过PI3P和曲率感应基序靶向自噬体。
DOI：
10.1016/j.devcel.2015.08.010
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发表时间：
2015-09-14
影响因子：
11.8
通讯作者：
Reinisch KM
中科院分区：
文献类型：
--
作者：
Horenkamp FA;Kauffman KJ;Kohler LJ;Sherwood RK;Krueger KP;Shteyn V;Roy CR;Melia TJ;Reinisch KM
自噬是一种保守的膜运输途径，用于摧毁进入细胞胞浆的病原体。胞内病原体嗜肺军团菌通过将效应蛋白RavZ传递到宿主胞浆中来干扰自噬。RavZ通过从自噬前结构中裂解膜连接的Atg8/Lc3蛋白来发挥作用。其非凡的效率允许微量的RavZ阻止细胞内的自噬。为了了解RavZ是如何以自噬前体为靶标并仅特异性作用于膜相关的Atg8蛋白，我们阐明了它的结构。发现了一个与ULP家族脱泛素酶样酶折叠相关的催化结构域和一个C端的PI3P结合模块。RavZ通过PI3P结合模块和催化结构域螺旋靶向自噬小体，并优先结合高曲率膜，使其定位于自噬小体中间膜中的高弯曲结构域。RavZ膜的相互作用增强了底物的亲和力，为界面激活提供了一种机制，宿主自噬蛋白也可以利用这种机制只与脂化的Atg8蛋白结合。
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 preautophagosomal structures. Its remarkable efficiency allows minute quantities of RavZ to block autophagy throughout the cell. To understand how RavZ targets preautophagosomes 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 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 may also be used by host autophagy proteins engaging only lipidated Atg8 proteins.