Structural insights into caspase ADPR deacylization catalyzed by a bacterial effector and host calmodulin

文献类型： 外文期刊

第一作者： Zhang, Kuo

作者： Zhang, Kuo;Tian, Miao;Wang, Zhao;Wu, Qiulan;Fu, Yang;Zhang, Kuo;Peng, Ting;Tao, Xinyuan;Tian, Miao;Hu, Shufan;Pan, Xing;Xue, Juan;Li, Shan;Peng, Ting;Tao, Xinyuan;Li, Yanxin;Ma, Shuaifei;Hu, Shufan;Pan, Xing;Xue, Juan;Luo, Jiwei;Li, Shan;Peng, Ting;Tao, Xinyuan;Li, Yanxin;Ma, Shuaifei;Hu, Shufan;Pan, Xing;Xue, Juan;Luo, Jiwei;Li, Shan;Peng, Ting;Tao, Xinyuan;Li, Yanxin;Ma, Shuaifei;Hu, Shufan;Li, Shan;Peng, Ting;Tao, Xinyuan;Li, Yanxin;Ma, Shuaifei;Hu, Shufan

作者机构：

期刊名称：MOLECULAR CELL （ 影响因子：16.0； 五年影响因子：18.4 ）

ISSN： 1097-2765

年卷期： 2022 年 82 卷 24 期

页码：

收录情况： SCI

摘要： Programmed cell death and caspase proteins play a pivotal role in host innate immune response combating pathogen infections. Blocking cell death is employed by many bacterial pathogens as a universal virulence strategy. CopC family type III effectors, including CopC from an environmental pathogen Chromobacterium violaceum, utilize calmodulin (CaM) as a co-factor to inactivate caspases by arginine ADPR deacylization. However, the molecular basis of the catalytic and substrate/co-factor binding mechanism is unknown. Here, we determine successive cryo-EM structures of CaM-CopC-caspase-3 ternary complex in pre -reac-tion, transition, and post-reaction states, which elucidate a multistep enzymatic mechanism of CopC-cata-lyzed ADPR deacylization. Moreover, we capture a snapshot of the detachment of modified caspase-3 from CopC. These structural insights are validated by mutagenesis analyses of CopC-mediated ADPR de-acylization in vitro and animal infection in vivo. Our study offers a structural framework for understanding the molecular basis of arginine ADPR deacylization catalyzed by the CopC family.

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