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-Structure paper
タイトル | Structural insights into caspase ADPR deacylization catalyzed by a bacterial effector and host calmodulin. |
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ジャーナル・号・ページ | Mol Cell, Vol. 82, Issue 24, Page 4712-44726.e7, Year 2022 |
掲載日 | 2022年12月15日 |
著者 | Kuo Zhang / Ting Peng / Xinyuan Tao / Miao Tian / Yanxin Li / Zhao Wang / Shuaifei Ma / Shufan Hu / Xing Pan / Juan Xue / Jiwei Luo / Qiulan Wu / Yang Fu / Shan Li / |
PubMed 要旨 | 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 ...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-reaction, transition, and post-reaction states, which elucidate a multistep enzymatic mechanism of CopC-catalyzed 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 deacylization 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. |
リンク | Mol Cell / PubMed:36423631 |
手法 | EM (単粒子) |
解像度 | 3.18 - 3.45 Å |
構造データ | EMDB-33310, PDB-7xn4: EMDB-33311, PDB-7xn5: EMDB-33312, PDB-7xn6: |
化合物 | ChemComp-NAD: ChemComp-NCA: ChemComp-APR: |
由来 |
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キーワード | TOXIN / type III secretion system / Chromobacterium violaceum / caspase-3 / new PTM / programmed cell deathA / DP-ribosylation / ADPR-deacylization |