+Open data
-Basic information
Entry | Database: PDB / ID: 4uf2 | ||||||
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Title | Deerpox virus DPV022 in complex with Bax BH3 | ||||||
Components |
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Keywords | VIRAL PROTEIN / DEERPOX VIRUS / APOPTOSIS / BCL-2 / BAX BH3 | ||||||
Function / homology | Function and homology information T cell homeostatic proliferation / release of matrix enzymes from mitochondria / positive regulation of developmental pigmentation / protein insertion into mitochondrial membrane / BAX complex / B cell receptor apoptotic signaling pathway / positive regulation of reproductive process / positive regulation of motor neuron apoptotic process / regulation of mammary gland epithelial cell proliferation / spermatid differentiation ...T cell homeostatic proliferation / release of matrix enzymes from mitochondria / positive regulation of developmental pigmentation / protein insertion into mitochondrial membrane / BAX complex / B cell receptor apoptotic signaling pathway / positive regulation of reproductive process / positive regulation of motor neuron apoptotic process / regulation of mammary gland epithelial cell proliferation / spermatid differentiation / Activation, translocation and oligomerization of BAX / positive regulation of B cell apoptotic process / development of secondary sexual characteristics / NTRK3 as a dependence receptor / Sertoli cell proliferation / positive regulation of apoptotic DNA fragmentation / B cell homeostatic proliferation / glycosphingolipid metabolic process / positive regulation of mitochondrial membrane permeability involved in apoptotic process / retinal cell programmed cell death / B cell negative selection / BAK complex / activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c / apoptotic process involved in blood vessel morphogenesis / mitochondrial fragmentation involved in apoptotic process / negative regulation of endoplasmic reticulum calcium ion concentration / regulation of mitochondrial membrane permeability involved in programmed necrotic cell death / apoptotic process involved in embryonic digit morphogenesis / mitochondrial permeability transition pore complex / Release of apoptotic factors from the mitochondria / post-embryonic camera-type eye morphogenesis / establishment or maintenance of transmembrane electrochemical gradient / apoptotic process involved in mammary gland involution / Transcriptional regulation by RUNX2 / positive regulation of apoptotic process involved in mammary gland involution / regulation of nitrogen utilization / B cell apoptotic process / endoplasmic reticulum calcium ion homeostasis / positive regulation of endoplasmic reticulum unfolded protein response / fertilization / positive regulation of epithelial cell apoptotic process / calcium ion transport into cytosol / motor neuron apoptotic process / mitochondrial fusion / channel activity / Bcl-2 family protein complex / epithelial cell apoptotic process / myeloid cell homeostasis / hypothalamus development / positive regulation of calcium ion transport into cytosol / thymocyte apoptotic process / pore complex / BH3 domain binding / germ cell development / odontogenesis of dentin-containing tooth / apoptotic mitochondrial changes / positive regulation of IRE1-mediated unfolded protein response / positive regulation of release of cytochrome c from mitochondria / negative regulation of mitochondrial membrane potential / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / vagina development / B cell homeostasis / negative regulation of apoptotic signaling pathway / host cell mitochondrion / intrinsic apoptotic signaling pathway by p53 class mediator / extrinsic apoptotic signaling pathway via death domain receptors / host cell membrane / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / response to axon injury / ectopic germ cell programmed cell death / cellular response to unfolded protein / blood vessel remodeling / Pyroptosis / supramolecular fiber organization / negative regulation of peptidyl-serine phosphorylation / positive regulation of intrinsic apoptotic signaling pathway / negative regulation of fibroblast proliferation / extrinsic apoptotic signaling pathway / ovarian follicle development / release of sequestered calcium ion into cytosol / homeostasis of number of cells within a tissue / extrinsic apoptotic signaling pathway in absence of ligand / response to salt stress / Hsp70 protein binding / intrinsic apoptotic signaling pathway / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / positive regulation of release of sequestered calcium ion into cytosol / release of cytochrome c from mitochondria / regulation of mitochondrial membrane potential / negative regulation of protein binding / kidney development / response to gamma radiation / apoptotic signaling pathway / neuron migration / positive regulation of protein-containing complex assembly / response to toxic substance / cerebral cortex development / cellular response to virus / activation of cysteine-type endopeptidase activity involved in apoptotic process / cellular response to UV Similarity search - Function | ||||||
Biological species | Deerpox virus Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 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 | 4uf2.cif.gz | 44 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4uf2.ent.gz | 30.9 KB | Display | PDB format |
PDBx/mmJSON format | 4uf2.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/uf/4uf2 ftp://data.pdbj.org/pub/pdb/validation_reports/uf/4uf2 | HTTPS FTP |
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-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 19633.271 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: 3152.553 Da / Num. of mol.: 1 / Fragment: BH3, UNP RESIDUES 50-77 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: Q07812 |
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: 1.99 Å3/Da / Density % sol: 81.6 % Description: RESIDUES FROM 1 AND 2 AND FROM 138 TO 155 ARE DISORDERED IN DPV022 AND IN BAX BH3 THE RESIDUES FROM 51 TO 56 AND 76 TO 78 ARE MISSING. |
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Crystal grow | pH: 6 Details: 20% PEG 6000, 0.2M MES PH 6.0, 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: 0.93537 |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Oct 9, 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: 0.93537 Å / Relative weight: 1 |
Reflection | Resolution: 3→92.48 Å / Num. obs: 4297 / % possible obs: 100 % / Observed criterion σ(I): 2 / Redundancy: 6.9 % / Biso Wilson estimate: 76.19 Å2 / Rmerge(I) obs: 0.14 / Net I/σ(I): 10.2 |
Reflection shell | Resolution: 3→3.18 Å / Redundancy: 7.2 % / Rmerge(I) obs: 1.1 / Mean I/σ(I) obs: 1.7 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: DPV022_BIM Resolution: 3→46.24 Å / SU ML: 0.03 / σ(F): 1.35 / Phase error: 28.61 / Stereochemistry target values: ML
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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: 81.6 Å2 | ||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 3→46.24 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 3.0005→46.246 Å
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