+Open data
-Basic information
Entry | Database: PDB / ID: 5tzp | ||||||
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Title | Crystal structure of FPV039:Bik BH3 complex | ||||||
Components |
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Keywords | APOPTOSIS / Bcl-2 / fowlpox / poxvirus / BH3-only | ||||||
Function / homology | Function and homology information host cell mitochondrion / regulation of apoptotic process / membrane => GO:0016020 / apoptotic process Similarity search - Function | ||||||
Biological species | Fowlpox virus Gallus gallus (chicken) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.35 Å | ||||||
Authors | Anasir, M.I. / Kvansakul, M. | ||||||
Funding support | Australia, 1items
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Citation | Journal: J Biol Chem / Year: 2017 Title: Structural basis of apoptosis inhibition by the fowlpox virus protein FPV039. Authors: Mohd Ishtiaq Anasir / Sofia Caria / Michael A Skinner / Marc Kvansakul / Abstract: Programmed cell death or apoptosis of infected host cells is an important defense mechanism in response to viral infections. This process is regulated by proapoptotic and prosurvival members of the B- ...Programmed cell death or apoptosis of infected host cells is an important defense mechanism in response to viral infections. This process is regulated by proapoptotic and prosurvival members of the B-cell lymphoma 2 (Bcl-2) protein family. To counter premature death of a virus-infected cell, poxviruses use a range of different molecular strategies including the mimicry of prosurvival Bcl-2 proteins. One such viral prosurvival protein is the fowlpox virus protein FPV039, which is a potent apoptosis inhibitor, but the precise molecular mechanism by which FPV039 inhibits apoptosis is unknown. To understand how fowlpox virus inhibits apoptosis, we examined FPV039 using isothermal titration calorimetry, small-angle X-ray scattering, and X-ray crystallography. Here, we report that the fowlpox virus prosurvival protein FPV039 promiscuously binds to cellular proapoptotic Bcl-2 and engages all major proapoptotic Bcl-2 proteins. Unlike other identified viral Bcl-2 proteins to date, FPV039 engaged with cellular proapoptotic Bcl-2 with affinities comparable with those of Bcl-2's endogenous cellular counterparts. Structural studies revealed that FPV039 adopts the conserved Bcl-2 fold observed in cellular prosurvival Bcl-2 proteins and closely mimics the structure of the prosurvival Bcl-2 family protein Mcl-1. Our findings suggest that FPV039 is a pan-Bcl-2 protein inhibitor that can engage all host BH3-only proteins, as well as Bcl-2-associated X, apoptosis regulator (Bax) and Bcl-2 antagonist/killer (Bak) proteins to inhibit premature apoptosis of an infected host cell. This work therefore provides a mechanistic platform to better understand FPV039-mediated apoptosis inhibition. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5tzp.cif.gz | 119.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5tzp.ent.gz | 94.4 KB | Display | PDB format |
PDBx/mmJSON format | 5tzp.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5tzp_validation.pdf.gz | 459.4 KB | Display | wwPDB validaton report |
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Full document | 5tzp_full_validation.pdf.gz | 462.2 KB | Display | |
Data in XML | 5tzp_validation.xml.gz | 11.8 KB | Display | |
Data in CIF | 5tzp_validation.cif.gz | 16.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tz/5tzp ftp://data.pdbj.org/pub/pdb/validation_reports/tz/5tzp | 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
#1: Protein | Mass: 17251.646 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Fowlpox virus (strain NVSL) / Strain: NVSL / Gene: FPV039 Production host: Escherichia coli-Pichia pastoris shuttle vector pPpARG4 (others) Strain (production host): DE3 / References: UniProt: Q9J5G4 | ||||
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#2: Protein/peptide | Mass: 2778.129 Da / Num. of mol.: 1 / Fragment: UNP residues 43-67 / Source method: obtained synthetically / Source: (synth.) Gallus gallus (chicken) / References: UniProt: E1C005 | ||||
#3: Chemical | ChemComp-EDO / #4: Chemical | ChemComp-SO4 / #5: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.12 Å3/Da / Density % sol: 42.2 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion / pH: 6.8 / Details: 0.2M Lithium Chloride, 20% w/v PEG 3350 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX2 / Wavelength: 0.9537 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: May 4, 2016 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9537 Å / Relative weight: 1 |
Reflection | Resolution: 1.35→47.85 Å / Num. obs: 36707 / % possible obs: 100 % / Redundancy: 14.5 % / Biso Wilson estimate: 11.8 Å2 / CC1/2: 1 / Rmerge(I) obs: 0.07 / Net I/σ(I): 24.1 |
Reflection shell | Resolution: 1.35→1.37 Å / Redundancy: 13.6 % / Rmerge(I) obs: 1.6 / Mean I/σ(I) obs: 1.7 / CC1/2: 0.598 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: FPV039 Resolution: 1.35→40.229 Å / SU ML: 0.14 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 16.12
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.35→40.229 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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