+Open data
-Basic information
Entry | Database: PDB / ID: 4uf1 | |||||||||
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Title | Deerpox virus DPV022 in complex with Bak BH3 | |||||||||
Components |
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Keywords | VIRAL PROTEIN / DEERPOX VIRUS / APOPTOSIS / BCL-2 / BAK BH3 | |||||||||
Function / homology | Function and homology information Activation and oligomerization of BAK protein / response to mycotoxin / B cell negative selection / BAK complex / BH domain binding / apoptotic process involved in blood vessel morphogenesis / response to fungus / negative regulation of endoplasmic reticulum calcium ion concentration / limb morphogenesis / Release of apoptotic factors from the mitochondria ...Activation and oligomerization of BAK protein / response to mycotoxin / B cell negative selection / BAK complex / BH domain binding / apoptotic process involved in blood vessel morphogenesis / response to fungus / negative regulation of endoplasmic reticulum calcium ion concentration / limb morphogenesis / Release of apoptotic factors from the mitochondria / post-embryonic camera-type eye morphogenesis / endocrine pancreas development / establishment or maintenance of transmembrane electrochemical gradient / positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway / B cell apoptotic process / negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway / activation of cysteine-type endopeptidase activity / endoplasmic reticulum calcium ion homeostasis / positive regulation of endoplasmic reticulum unfolded protein response / regulation of mitochondrial membrane permeability / calcium ion transport into cytosol / response to UV-C / fibroblast apoptotic process / mitochondrial fusion / Bcl-2 family protein complex / myeloid cell homeostasis / positive regulation of calcium ion transport into cytosol / porin activity / pore complex / thymocyte apoptotic process / negative regulation of release of cytochrome c from mitochondria / negative regulation of peptidyl-serine phosphorylation / positive regulation of IRE1-mediated unfolded protein response / positive regulation of release of cytochrome c from mitochondria / vagina development / positive regulation of proteolysis / B cell homeostasis / host cell mitochondrion / host cell membrane / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / cellular response to unfolded protein / blood vessel remodeling / Pyroptosis / animal organ regeneration / extrinsic apoptotic signaling pathway in absence of ligand / heat shock protein binding / intrinsic apoptotic signaling pathway / release of cytochrome c from mitochondria / regulation of mitochondrial membrane potential / epithelial cell proliferation / establishment of localization in cell / response to gamma radiation / apoptotic signaling pathway / positive regulation of protein-containing complex assembly / response to hydrogen peroxide / response to organic cyclic compound / cellular response to mechanical stimulus / intrinsic apoptotic signaling pathway in response to DNA damage / cellular response to UV / protein-folding chaperone binding / regulation of apoptotic process / response to ethanol / mitochondrial outer membrane / transmembrane transporter binding / regulation of cell cycle / response to xenobiotic stimulus / positive regulation of apoptotic process / protein heterodimerization activity / negative regulation of cell population proliferation / negative regulation of gene expression / apoptotic process / protein-containing complex binding / endoplasmic reticulum / protein homodimerization activity / mitochondrion / identical protein binding / membrane / metal ion binding / cytosol Similarity search - Function | |||||||||
Biological species | Deerpox virus Homo sapiens (human) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.3 Å | |||||||||
Authors | Burton, D.R. / Kvansakul, M. | |||||||||
Citation | Journal: Acta Crystallogr D Biol Crystallogr / Year: 2015 Title: Structural basis of Deerpox virus-mediated inhibition of apoptosis. Authors: Denis R Burton / Sofia Caria / Bevan Marshall / Michele Barry / Marc Kvansakul / Abstract: Apoptosis is a key innate defence mechanism to eliminate virally infected cells. To counteract premature host-cell apoptosis, poxviruses have evolved numerous molecular strategies, including the use ...Apoptosis is a key innate defence mechanism to eliminate virally infected cells. To counteract premature host-cell apoptosis, poxviruses have evolved numerous molecular strategies, including the use of Bcl-2 proteins, to ensure their own survival. Here, it is reported that the Deerpox virus inhibitor of apoptosis, DPV022, only engages a highly restricted set of death-inducing Bcl-2 proteins, including Bim, Bax and Bak, with modest affinities. Structural analysis reveals that DPV022 adopts a Bcl-2 fold with a dimeric domain-swapped topology and binds pro-death Bcl-2 proteins via two conserved ligand-binding grooves found on opposite sides of the dimer. Structures of DPV022 bound to Bim, Bak and Bax BH3 domains reveal that a partial obstruction of the binding groove is likely to be responsible for the modest affinities of DPV022 for BH3 domains. These findings reveal that domain-swapped dimeric Bcl-2 folds are not unusual and may be found more widely in viruses. Furthermore, the modest affinities of DPV022 for pro-death Bcl-2 proteins suggest that two distinct classes of anti-apoptotic viral Bcl-2 proteins exist: those that are monomeric and tightly bind a range of death-inducing Bcl-2 proteins, and others such as DPV022 that are dimeric and only bind a very limited number of death-inducing Bcl-2 proteins with modest affinities. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4uf1.cif.gz | 107 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4uf1.ent.gz | 84 KB | Display | PDB format |
PDBx/mmJSON format | 4uf1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4uf1_validation.pdf.gz | 317.5 KB | Display | wwPDB validaton report |
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Full document | 4uf1_full_validation.pdf.gz | 317.6 KB | Display | |
Data in XML | 4uf1_validation.xml.gz | 8 KB | Display | |
Data in CIF | 4uf1_validation.cif.gz | 10.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/uf/4uf1 ftp://data.pdbj.org/pub/pdb/validation_reports/uf/4uf1 | HTTPS FTP |
-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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Components on special symmetry positions |
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-Components
#1: Protein | Mass: 19632.287 Da / Num. of mol.: 1 / Fragment: BCL-2, UNP RESIDUES 1-155 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Deerpox virus (strain W-1170-84) / Strain: W-1170-84 / Gene: DpV84gp022 / Plasmid: pDUET / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q08FF8, UniProt: Q08FX8*PLUS |
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#2: Protein/peptide | Mass: 2882.151 Da / Num. of mol.: 1 / Fragment: BH3, UNP RESIDUES 67-92 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: Q16611 |
#3: Chemical | ChemComp-SO4 / |
#4: Water | ChemComp-HOH / |
Sequence details | STRUCTURE FROM CONSTRUCT RESIDUES 1-155 |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.03 Å3/Da / Density % sol: 39.4 % Description: THE STARTING MODEL WAS USED WITHOUT THE BIMBH3 LIGAND |
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Crystal grow | pH: 5.5 Details: 17% PEG 8000, 0.2M MES PH 5.5, 0.2M AMMONIUM SULPHATE |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX2 / Wavelength: 0.9537 |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Jun 25, 2013 / Details: SILICON MIRRORS (ADAPTIVE AND U-BENT) |
Radiation | Monochromator: DOUBLE CRYSTAL MONOCHROMATOR (SI111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9537 Å / Relative weight: 1 |
Reflection | Resolution: 2.3→41.71 Å / Num. obs: 9129 / % possible obs: 97.7 % / Observed criterion σ(I): 2 / Redundancy: 5.7 % / Biso Wilson estimate: 32.8 Å2 / Rmerge(I) obs: 0.1 / Net I/σ(I): 10.9 |
Reflection shell | Resolution: 2.3→2.39 Å / Redundancy: 5.8 % / Rmerge(I) obs: 0.58 / Mean I/σ(I) obs: 3.1 / % possible all: 99 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: DPV022_BIM Resolution: 2.3→41.707 Å / SU ML: 0.24 / σ(F): 1.36 / Phase error: 22.37 / Stereochemistry target values: ML Details: RESIDUES FROM 1 AND 2 AND FROM 138 TO 155 ARE MISSING IN DPV022. IN BAK,THE RESIDUES 67 AND 68 AS WELL AS 91 AND 92
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 48.7 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.3→41.707 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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