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- PDB-7xn4: Cryo-EM structure of CopC-CaM-caspase-3 with NAD+ -

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Basic information

Entry
Database: PDB / ID: 7xn4
TitleCryo-EM structure of CopC-CaM-caspase-3 with NAD+
Components
  • Arginine ADP-riboxanase CopC
  • Calmodulin-1
  • Caspase-3Caspase 3
KeywordsTOXIN / 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 / caspase-3 / Stimulation of the cell death response by PAK-2p34 / phospholipase A2 activator activity / anterior neural tube closure / intrinsic apoptotic signaling pathway in response to osmotic stress / leukocyte apoptotic process / positive regulation of pyroptotic inflammatory response ...: / Lyases; Carbon-nitrogen lyases; Other carbon-nitrogen lyases / ADP-riboxanase activity / caspase-3 / Stimulation of the cell death response by PAK-2p34 / phospholipase A2 activator activity / anterior neural tube closure / intrinsic apoptotic signaling pathway in response to osmotic stress / leukocyte apoptotic process / positive regulation of pyroptotic inflammatory response / glial cell apoptotic process / NADE modulates death signalling / luteolysis / response to cobalt ion / cysteine-type endopeptidase activity involved in apoptotic signaling pathway / death-inducing signaling complex / cyclin-dependent protein serine/threonine kinase inhibitor activity / cellular response to staurosporine / Apoptosis induced DNA fragmentation / cysteine-type endopeptidase activity involved in execution phase of apoptosis / Caspase activation via Dependence Receptors in the absence of ligand / Apoptotic cleavage of cell adhesion proteins / death receptor binding / SMAC, XIAP-regulated apoptotic response / axonal fasciculation / Activation of caspases through apoptosome-mediated cleavage / Signaling by Hippo / SMAC (DIABLO) binds to IAPs / SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes / cysteine-type endopeptidase activity involved in apoptotic process / CaM pathway / Cam-PDE 1 activation / Sodium/Calcium exchangers / Calmodulin induced events / fibroblast apoptotic process / execution phase of apoptosis / negative regulation of cytokine production / Reduction of cytosolic Ca++ levels / epithelial cell apoptotic process / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / Activation of Ca-permeable Kainate Receptor / Loss of phosphorylation of MECP2 at T308 / platelet formation / CREB1 phosphorylation through the activation of Adenylate Cyclase / PKA activation / negative regulation of high voltage-gated calcium channel activity / CaMK IV-mediated phosphorylation of CREB / Glycogen breakdown (glycogenolysis) / organelle localization by membrane tethering / negative regulation of calcium ion export across plasma membrane / Activation of RAC1 downstream of NMDARs / mitochondrion-endoplasmic reticulum membrane tethering / CLEC7A (Dectin-1) induces NFAT activation / Other interleukin signaling / regulation of cardiac muscle cell action potential / autophagosome membrane docking / positive regulation of amyloid-beta formation / positive regulation of ryanodine-sensitive calcium-release channel activity / regulation of cell communication by electrical coupling involved in cardiac conduction / Negative regulation of NMDA receptor-mediated neuronal transmission / negative regulation of peptidyl-threonine phosphorylation / Synthesis of IP3 and IP4 in the cytosol / Apoptotic cleavage of cellular proteins / negative regulation of B cell proliferation / Unblocking of NMDA receptors, glutamate binding and activation / pyroptotic inflammatory response / Phase 0 - rapid depolarisation / protein phosphatase activator activity / T cell homeostasis / RHO GTPases activate PAKs / negative regulation of activated T cell proliferation / positive regulation of cyclic-nucleotide phosphodiesterase activity / positive regulation of phosphoprotein phosphatase activity / Ion transport by P-type ATPases / neurotrophin TRK receptor signaling pathway / B cell homeostasis / Long-term potentiation / Uptake and function of anthrax toxins / protein maturation / Regulation of MECP2 expression and activity / Calcineurin activates NFAT / catalytic complex / negative regulation of cell cycle / response to X-ray / DARPP-32 events / detection of calcium ion / negative regulation of ryanodine-sensitive calcium-release channel activity / Smooth Muscle Contraction / regulation of macroautophagy / Caspase-mediated cleavage of cytoskeletal proteins / RHO GTPases activate IQGAPs / regulation of cardiac muscle contraction / calcium channel inhibitor activity / cellular response to interferon-beta / cell fate commitment / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / response to amino acid / Pyroptosis / Protein methylation / response to tumor necrosis factor
Similarity search - Function
Arginine ADP-riboxanase OspC1-3 / Shigella flexneri OspC protein / Ankyrin repeat / Peptidase family C14A, His active site / Caspase family histidine active site. / Peptidase C14, caspase non-catalytic subunit p10 / Peptidase family C14A, cysteine active site / Caspase family cysteine active site. / Caspase family p10 domain profile. / Peptidase C14A, caspase catalytic domain ...Arginine ADP-riboxanase OspC1-3 / Shigella flexneri OspC protein / Ankyrin repeat / Peptidase family C14A, His active site / Caspase family histidine active site. / Peptidase C14, caspase non-catalytic subunit p10 / Peptidase family C14A, cysteine active site / Caspase family cysteine active site. / Caspase family p10 domain profile. / Peptidase C14A, caspase catalytic domain / Caspase, interleukin-1 beta converting enzyme (ICE) homologues / Peptidase C14, p20 domain / Caspase family p20 domain profile. / : / Caspase domain / Caspase-like domain superfamily / EF-hand domain pair / Ankyrin repeat profile. / Ankyrin repeat region circular profile. / Ankyrin repeat / Ankyrin repeat-containing domain superfamily / EF-hand, calcium binding motif / EF-Hand 1, calcium-binding site / EF-hand calcium-binding domain. / EF-hand calcium-binding domain profile. / EF-hand domain / EF-hand domain pair
Similarity search - Domain/homology
NICOTINAMIDE-ADENINE-DINUCLEOTIDE / Calmodulin-1 / Caspase-3 / Arginine ADP-riboxanase CopC
Similarity search - Component
Biological speciesHomo sapiens (human)
Chromobacterium violaceum (bacteria)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.35 Å
AuthorsZhang, 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 support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: 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
DepositionApr 28, 2022Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Dec 14, 2022Provider: repository / Type: Initial release
Revision 1.1Dec 28, 2022Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Caspase-3
B: Arginine ADP-riboxanase CopC
C: Caspase-3
D: Calmodulin-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)133,8055
Polymers133,1424
Non-polymers6631
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein Caspase-3 / Caspase 3 / CASP-3 / Apopain / Cysteine protease CPP32 / CPP-32 / Protein Yama / SREBP cleavage activity 1 / SCA-1


Mass: 31651.938 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 Arginine ADP-riboxanase CopC


Mass: 52985.516 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Chromobacterium violaceum (bacteria)
Strain: ATCC 12472 / DSM 30191 / JCM 1249 / NBRC 12614 / NCIMB 9131 / NCTC 9757
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 Calmodulin-1 /


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-NAD / NICOTINAMIDE-ADENINE-DINUCLEOTIDE / Nicotinamide adenine dinucleotide


Mass: 663.425 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H27N7O14P2 / Comment: NAD*YM
Has ligand of interestN

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Cryo-EM structure of CopC-CaM-caspase-3 with NAD+ / Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Bacteria Latreille et al. 1825 (Bacteria stick insect)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2500 nm / Nominal defocus min: 500 nm
Image recordingElectron dose: 40 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k)

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Processing

SoftwareName: PHENIX / Version: 1.19.2_4158: / Classification: refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.35 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 102210 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0037005
ELECTRON MICROSCOPYf_angle_d0.5869434
ELECTRON MICROSCOPYf_dihedral_angle_d8.118939
ELECTRON MICROSCOPYf_chiral_restr0.0411009
ELECTRON MICROSCOPYf_plane_restr0.0051219

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