+Open data
-Basic information
Entry | Database: PDB / ID: 7xn6 | |||||||||
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Title | Cryo-EM structure of CopC-CaM-caspase-3 with ADPR-deacylization | |||||||||
Components |
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Keywords | TOXIN / type III secretion system / Chromobacterium violaceum / caspase-3 / new PTM / programmed cell deathA / DP-ribosylation / ADPR-deacylization | |||||||||
Function / homology | Function and homology information Lyases; Carbon-nitrogen lyases; Other carbon-nitrogen lyases / ADP-riboxanase activity / symbiont-mediated perturbation of host programmed cell death / anterior neural tube closure / Stimulation of the cell death response by PAK-2p34 / caspase-3 / phospholipase A2 activator activity / intrinsic apoptotic signaling pathway in response to osmotic stress / leukocyte apoptotic process / glial cell apoptotic process ...Lyases; Carbon-nitrogen lyases; Other carbon-nitrogen lyases / ADP-riboxanase activity / symbiont-mediated perturbation of host programmed cell death / anterior neural tube closure / Stimulation of the cell death response by PAK-2p34 / caspase-3 / phospholipase A2 activator activity / intrinsic apoptotic signaling pathway in response to osmotic stress / leukocyte apoptotic process / glial cell apoptotic process / positive regulation of pyroptotic inflammatory response / NADE modulates death signalling / response to cobalt ion / luteolysis / : / death-inducing signaling complex / cellular response to staurosporine / cyclin-dependent protein serine/threonine kinase inhibitor activity / Apoptosis induced DNA fragmentation / : / Apoptotic cleavage of cell adhesion proteins / Caspase activation via Dependence Receptors in the absence of ligand / death receptor binding / SMAC, XIAP-regulated apoptotic response / axonal fasciculation / Activation of caspases through apoptosome-mediated cleavage / : / fibroblast apoptotic process / Signaling by Hippo / SMAC (DIABLO) binds to IAPs / SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes / CaM pathway / Cam-PDE 1 activation / Sodium/Calcium exchangers / Reduction of cytosolic Ca++ levels / Calmodulin induced events / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / Activation of Ca-permeable Kainate Receptor / Loss of phosphorylation of MECP2 at T308 / negative regulation of cytokine production / epithelial cell apoptotic process / CREB1 phosphorylation through the activation of Adenylate Cyclase / PKA activation / platelet formation / organelle localization by membrane tethering / negative regulation of high voltage-gated calcium channel activity / CaMK IV-mediated phosphorylation of CREB / autophagosome membrane docking / mitochondrion-endoplasmic reticulum membrane tethering / Glycogen breakdown (glycogenolysis) / positive regulation of cyclic-nucleotide phosphodiesterase activity / execution phase of apoptosis / negative regulation of calcium ion export across plasma membrane / CLEC7A (Dectin-1) induces NFAT activation / Other interleukin signaling / positive regulation of amyloid-beta formation / Activation of RAC1 downstream of NMDARs / regulation of cardiac muscle cell action potential / pyroptotic inflammatory response / positive regulation of ryanodine-sensitive calcium-release channel activity / regulation of cell communication by electrical coupling involved in cardiac conduction / Synthesis of IP3 and IP4 in the cytosol / Apoptotic cleavage of cellular proteins / negative regulation of peptidyl-threonine phosphorylation / Negative regulation of NMDA receptor-mediated neuronal transmission / negative regulation of B cell proliferation / T cell homeostasis / Phase 0 - rapid depolarisation / Unblocking of NMDA receptors, glutamate binding and activation / B cell homeostasis / negative regulation of ryanodine-sensitive calcium-release channel activity / adenylate cyclase activator activity / protein phosphatase activator activity / negative regulation of activated T cell proliferation / RHO GTPases activate PAKs / Ion transport by P-type ATPases / : / neurotrophin TRK receptor signaling pathway / protein maturation / Uptake and function of anthrax toxins / Long-term potentiation / Regulation of MECP2 expression and activity / Calcineurin activates NFAT / negative regulation of cell cycle / catalytic complex / response to X-ray / DARPP-32 events / regulation of cardiac muscle contraction / detection of calcium ion / Pyroptosis / Smooth Muscle Contraction / cell fate commitment / regulation of ryanodine-sensitive calcium-release channel activity / response to amino acid / cellular response to interferon-beta / RHO GTPases activate IQGAPs / regulation of macroautophagy / Caspase-mediated cleavage of cytoskeletal proteins / response to tumor necrosis factor / calcium channel inhibitor activity Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) Chromobacterium violaceum (bacteria) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.45 Å | |||||||||
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. ...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. | |||||||||
Funding support | 1items
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Citation | Journal: Mol Cell / Year: 2022 Title: Structural insights into caspase ADPR deacylization catalyzed by a bacterial effector and host calmodulin. Authors: 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 / 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 ...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. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7xn6.cif.gz | 171.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7xn6.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 7xn6.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7xn6_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 7xn6_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 7xn6_validation.xml.gz | 40.6 KB | Display | |
Data in CIF | 7xn6_validation.cif.gz | 56.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xn/7xn6 ftp://data.pdbj.org/pub/pdb/validation_reports/xn/7xn6 | HTTPS FTP |
-Related structure data
Related structure data | 33312MC 7xn4C 7xn5C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 32175.195 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CASP3, CPP32 Production host: Bacteria Latreille et al. 1825 (Bacteria stick insect) References: UniProt: P42574, caspase-3 #2: Protein | | Mass: 52985.516 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Chromobacterium violaceum (bacteria) / Gene: copC, CV_2038 Production host: Bacteria Latreille et al. 1825 (Bacteria stick insect) References: UniProt: Q7NWF2, Lyases; Carbon-nitrogen lyases; Other carbon-nitrogen lyases #3: Protein | | Mass: 16852.545 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CALM1, CALM, CAM, CAM1 Production host: Bacteria Latreille et al. 1825 (Bacteria stick insect) References: UniProt: P0DP23 #4: Chemical | ChemComp-NCA / | Has ligand of interest | N | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Cryo-EM structure of CopC-CaM-caspase-3 with ADPR-deacylization Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Bacteria Latreille et al. 1825 (Bacteria stick insect) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.45 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 82876 / Symmetry type: POINT | ||||||||||||||||||||||||
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