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- PDB-5tzp: Crystal structure of FPV039:Bik BH3 complex -

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Basic information

Entry
Database: PDB / ID: 5tzp
TitleCrystal structure of FPV039:Bik BH3 complex
Components
  • Bcl-2-like protein FPV039
  • Bik
KeywordsAPOPTOSIS / 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
Bcl-2-interacting killer / Bcl2-interacting killer, BH3-domain containing / Apoptosis regulator, Bcl-2, BH1 motif, conserved site / Apoptosis regulator, Bcl-2 family BH1 motif signature. / Bcl-2, Bcl-2 homology region 1-3 / Bcl2-like / Apoptosis regulator proteins, Bcl-2 family / BCL2-like apoptosis inhibitors family profile. / Bcl-2-like superfamily
Similarity search - Domain/homology
Uncharacterized protein / Apoptosis regulator Bcl-2 homolog
Similarity search - Component
Biological speciesFowlpox virus
Gallus gallus (chicken)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.35 Å
AuthorsAnasir, M.I. / Kvansakul, M.
Funding support Australia, 1items
OrganizationGrant numberCountry
Australian Research Council (ARC)FT130101349 Australia
CitationJournal: 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
DepositionNov 22, 2016Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 3, 2017Provider: repository / Type: Initial release
Revision 1.1Jun 14, 2017Group: Database references / Category: citation
Item: _citation.country / _citation.journal_id_ASTM ..._citation.country / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title
Revision 1.2Jan 1, 2020Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.3Apr 3, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_conn
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr1_symmetry / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_conn.ptnr2_symmetry

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Bcl-2-like protein FPV039
B: Bik
hetero molecules


Theoretical massNumber of molelcules
Total (without water)21,04115
Polymers20,0302
Non-polymers1,01113
Water3,513195
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3040 Å2
ΔGint-57 kcal/mol
Surface area9510 Å2
MethodPISA
Unit cell
Length a, b, c (Å)47.848, 47.848, 74.303
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number78
Space group name H-MP43

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Components

#1: Protein Bcl-2-like protein FPV039


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
#2: Protein/peptide Bik


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 / 1,2-ETHANEDIOL / ETHYLENE GLYCOL / Ethylene glycol


Mass: 62.068 Da / Num. of mol.: 7 / Source method: obtained synthetically / Formula: C2H6O2
#4: Chemical
ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: SO4
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 195 / Source method: isolated from a natural source / Formula: H2O

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

CrystalDensity Matthews: 2.12 Å3/Da / Density % sol: 42.2 %
Crystal growTemperature: 293 K / Method: vapor diffusion / pH: 6.8 / Details: 0.2M Lithium Chloride, 20% w/v PEG 3350

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX2 / Wavelength: 0.9537 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: May 4, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9537 Å / Relative weight: 1
ReflectionResolution: 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 shellResolution: 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

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Processing

Software
NameVersionClassification
PHENIX(1.10_2155: ???)refinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod 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
RfactorNum. reflection% reflection
Rfree0.1716 1837 5 %
Rwork0.1468 --
obs0.1479 36707 100 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Refinement stepCycle: LAST / Resolution: 1.35→40.229 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1323 0 58 195 1576
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0241447
X-RAY DIFFRACTIONf_angle_d1.8311958
X-RAY DIFFRACTIONf_dihedral_angle_d20.092529
X-RAY DIFFRACTIONf_chiral_restr0.103212
X-RAY DIFFRACTIONf_plane_restr0.013239
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.35-1.38650.29971490.27152661X-RAY DIFFRACTION100
1.3865-1.42730.27041610.22662654X-RAY DIFFRACTION100
1.4273-1.47340.26771310.19752707X-RAY DIFFRACTION100
1.4734-1.52610.19521420.17862669X-RAY DIFFRACTION100
1.5261-1.58720.18891510.1632640X-RAY DIFFRACTION100
1.5872-1.65940.19541490.152677X-RAY DIFFRACTION100
1.6594-1.74690.18181670.13822613X-RAY DIFFRACTION100
1.7469-1.85630.13841370.13442707X-RAY DIFFRACTION100
1.8563-1.99960.12971020.12772730X-RAY DIFFRACTION100
1.9996-2.20090.17551550.12112662X-RAY DIFFRACTION100
2.2009-2.51930.14151420.12122700X-RAY DIFFRACTION100
2.5193-3.17390.17191260.14272706X-RAY DIFFRACTION100
3.1739-40.24640.15721250.15192744X-RAY DIFFRACTION100
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
12.131-0.13680.19212.7559-1.36683.6942-0.0011-0.055-0.35010.0138-0.00750.10430.4289-0.00830.01920.12730.00850.02240.0702-0.00770.1543-0.777315.4284-6.394
21.31570.9297-0.84021.7774-1.00331.6109-0.00220.05980.005-0.0172-0.00290.0764-0.0232-0.11990.01160.06430.00290.00180.0714-0.01330.11170.408727.9676-9.3004
32.1068-0.2115-1.31990.12870.11362.17140.1094-0.31510.139-0.0270.0609-0.2045-0.00010.5041-0.00570.13830.0145-0.01040.2179-0.02150.215215.987921.7173-2.9901
40.6639-0.5022-1.19450.50781.09092.83310.05290.0562-0.0188-0.036-0.02920.0563-0.0204-0.03370.05930.08220.0071-0.00420.0762-0.02170.11197.119322.4678-13.6667
51.8515-0.8825-1.04471.20090.43372.1738-0.152-0.1977-0.12150.14790.12590.0750.22280.09750.01480.08840.00610.01170.09230.00690.11342.226419.1472.0192
61.8057-2.04781.44032.327-1.61911.19460.27360.29540.00650.17-0.4693-1.0160.1360.83690.40560.27820.0487-0.03130.2707-0.00220.271225.392531.0464-4.5461
72.83320.38991.1161.0265-0.87441.52930.0936-0.35060.48390.011-0.220.2319-0.0961-0.45010.06280.1474-0.0324-0.00660.1828-0.0830.196511.516832.93590.4923
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 6 through 27 )
2X-RAY DIFFRACTION2chain 'A' and (resid 28 through 64 )
3X-RAY DIFFRACTION3chain 'A' and (resid 65 through 82 )
4X-RAY DIFFRACTION4chain 'A' and (resid 83 through 109 )
5X-RAY DIFFRACTION5chain 'A' and (resid 110 through 143 )
6X-RAY DIFFRACTION6chain 'B' and (resid 43 through 48 )
7X-RAY DIFFRACTION7chain 'B' and (resid 49 through 64 )

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