生物
半胱氨酸蛋白酶
上睑下垂
效应器
细胞生物学
蛋白酵素
程序性细胞死亡
紫红色杆菌
坏死性下垂
毒力
细胞凋亡
微生物学
遗传学
生物化学
酶
群体感应
基因
作者
Ting Peng,Xinyuan Tao,Zhujun Xia,Shufan Hu,Jian Xue,Qiuyu Zhu,Puyuan Xing,Qiang Zhang,Shan Li
出处
期刊:Molecular Cell
[Elsevier]
日期:2022-05-01
卷期号:82 (10): 1806-1820.e8
被引量:17
标识
DOI:10.1016/j.molcel.2022.03.010
摘要
Caspases are evolutionarily conserved cysteine proteases that are essential for regulating cell death and are involved in multiple development and disease processes, including immunity. Here, we show that the bacterial type III secretion system (T3SS) effector CopC (Chromobacterium outer protein C) from the environmental pathogen Chromobacterium violaceum attacks caspase-3/-7/-8/-9 by ADPR-deacylization to dysregulate programmed cell death, including apoptosis, necroptosis, and pyroptosis. This modification involves ADP-ribosylation- and deamination-mediated cyclization on Arg207 of caspase-3 by a mechanism that requires the eukaryote-specific protein calmodulin (CaM), leading to inhibition of caspase activity. The manipulation of cell death signaling by CopC is essential for the virulence of C. violaceum in a mouse infection model. CopC represents a family of enzymes existing in taxonomically diverse bacteria associated with a wide spectrum of eukaryotes ranging from humans to plants. The unique activity of CopC establishes a mechanism by which bacteria counteract host defenses through a previously unrecognized post-translational modification.
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