7XN4

Cryo-EM structure of CopC-CaM-caspase-3 with NAD+

Summary for 7XN4

• Entry DOI: 10.2210/pdb7xn4/pdb
• EMDB information: 33310
• Descriptor: Caspase-3, Arginine ADP-riboxanase CopC, Calmodulin-1, ... (4 entities in total)
• Functional Keywords: type iii secretion system, chromobacterium violaceum, caspase-3, new ptm, programmed cell deatha, dp-ribosylation, adpr-deacylization, toxin
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 133805.36

Authors

Zhang, K.,Peng, T.,Tao, X.Y.,Tian, M.,Li, Y.X.,Wang, Z.,Ma, S.F.,Hu, S.F.,Pan, X.,Xue, J.,Luo, J.W.,Wu, Q.L.,Fu, Y.,Li, S. (deposition date: 2022-04-28, release date: 2022-12-14, Last modification date: 2024-07-03)

Primary citation

Zhang, K.,Peng, T.,Tao, X.,Tian, M.,Li, Y.,Wang, Z.,Ma, S.,Hu, S.,Pan, X.,Xue, J.,Luo, J.,Wu, Q.,Fu, Y.,Li, S.
Structural insights into caspase ADPR deacylization catalyzed by a bacterial effector and host calmodulin.
Mol.Cell, 82:4712-4726.e7, 2022

PubMed Abstract: 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.

PubMed: 36423631
DOI: 10.1016/j.molcel.2022.10.032

Experimental method

ELECTRON MICROSCOPY (3.35 Å)