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Yorodumi- PDB-5d28: Complex of GM-CSF/IL-2 inhibition factor with Granulocyte-macroph... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5d28 | |||||||||
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Title | Complex of GM-CSF/IL-2 inhibition factor with Granulocyte-macrophage colony-stimulating factor | |||||||||
Components |
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Keywords | VIRAL PROTEIN / Signaling Protein / Cytokine / Host-pathogen interactions / Immunology | |||||||||
Function / homology | Function and homology information granulocyte macrophage colony-stimulating factor receptor binding / neutrophil differentiation / positive regulation of interleukin-23 production / positive regulation of macrophage derived foam cell differentiation / myeloid dendritic cell differentiation / granulocyte macrophage colony-stimulating factor receptor complex / granulocyte-macrophage colony-stimulating factor signaling pathway / positive regulation of leukocyte proliferation / cellular response to granulocyte macrophage colony-stimulating factor stimulus / positive regulation of podosome assembly ...granulocyte macrophage colony-stimulating factor receptor binding / neutrophil differentiation / positive regulation of interleukin-23 production / positive regulation of macrophage derived foam cell differentiation / myeloid dendritic cell differentiation / granulocyte macrophage colony-stimulating factor receptor complex / granulocyte-macrophage colony-stimulating factor signaling pathway / positive regulation of leukocyte proliferation / cellular response to granulocyte macrophage colony-stimulating factor stimulus / positive regulation of podosome assembly / cell surface receptor signaling pathway via JAK-STAT / monocyte differentiation / macrophage differentiation / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / embryonic placenta development / positive regulation of tyrosine phosphorylation of STAT protein / cytokine activity / growth factor activity / cell population proliferation / immune response / protein phosphorylation / intracellular membrane-bounded organelle / negative regulation of DNA-templated transcription / extracellular space Similarity search - Function | |||||||||
Biological species | Orf virus Ovis aries (sheep) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.845 Å | |||||||||
Authors | Felix, J. / Savvides, S.N. | |||||||||
Citation | Journal: Nat Commun / Year: 2016 Title: Structural basis of GM-CSF and IL-2 sequestration by the viral decoy receptor GIF. Authors: Jan Felix / Eaazhisai Kandiah / Steven De Munck / Yehudi Bloch / Gydo C P van Zundert / Kris Pauwels / Ann Dansercoer / Katka Novanska / Randy J Read / Alexandre M J J Bonvin / Bjorn ...Authors: Jan Felix / Eaazhisai Kandiah / Steven De Munck / Yehudi Bloch / Gydo C P van Zundert / Kris Pauwels / Ann Dansercoer / Katka Novanska / Randy J Read / Alexandre M J J Bonvin / Bjorn Vergauwen / Kenneth Verstraete / Irina Gutsche / Savvas N Savvides / Abstract: Subversion of the host immune system by viruses is often mediated by molecular decoys that sequester host proteins pivotal to mounting effective immune responses. The widespread mammalian pathogen ...Subversion of the host immune system by viruses is often mediated by molecular decoys that sequester host proteins pivotal to mounting effective immune responses. The widespread mammalian pathogen parapox Orf virus deploys GIF, a member of the poxvirus immune evasion superfamily, to antagonize GM-CSF (granulocyte macrophage colony-stimulating factor) and IL-2 (interleukin-2), two pleiotropic cytokines of the mammalian immune system. However, structural and mechanistic insights into the unprecedented functional duality of GIF have remained elusive. Here we reveal that GIF employs a dimeric binding platform that sequesters two copies of its target cytokines with high affinity and slow dissociation kinetics to yield distinct complexes featuring mutually exclusive interaction footprints. We illustrate how GIF serves as a competitive decoy receptor by leveraging binding hotspots underlying the cognate receptor interactions of GM-CSF and IL-2, without sharing any structural similarity with the cytokine receptors. Our findings contribute to the tracing of novel molecular mimicry mechanisms employed by pathogenic viruses. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5d28.cif.gz | 297.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5d28.ent.gz | 242.5 KB | Display | PDB format |
PDBx/mmJSON format | 5d28.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/d2/5d28 ftp://data.pdbj.org/pub/pdb/validation_reports/d2/5d28 | HTTPS FTP |
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-Related structure data
Related structure data | 4060C 5d22SC 1cq3S 2vgaS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
-Protein , 2 types, 4 molecules ADBC
#1: Protein | Mass: 27985.777 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Orf virus / Gene: GIF / Cell line (production host): HEK293 T / Production host: Homo sapiens (human) / References: UniProt: Q9J5U5 #2: Protein | Mass: 14426.386 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Ovis aries (sheep) / Gene: CSF2 / Production host: Escherichia coli (E. coli) / References: UniProt: P28773 |
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-Sugars , 3 types, 6 molecules
#3: Polysaccharide | Source method: isolated from a genetically manipulated source Source: (gene. exp.) Orf virus / Cell line (production host): HEK293T / Production host: Homo sapiens (human) #4: Polysaccharide | Source method: isolated from a genetically manipulated source Source: (gene. exp.) Orf virus / Cell line (production host): HEK293T / Production host: Homo sapiens (human) #5: Sugar | |
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-Non-polymers , 2 types, 19 molecules
#6: Chemical | #7: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION |
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-Sample preparation
Crystal | Density Matthews: 3.28 Å3/Da / Density % sol: 62.45 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6 Details: 0.15 M ammonium sulfate, 0.1 M MES pH 6.0, 24 % PEG 4000 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: PETRA III, EMBL c/o DESY / Beamline: P14 (MX2) / Wavelength: 0.976 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Oct 1, 2013 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.976 Å / Relative weight: 1 |
Reflection | Resolution: 2.84→50 Å / Num. obs: 25798 / % possible obs: 98.2 % / Redundancy: 6.9 % / Rsym value: 0.073 / Net I/σ(I): 20.39 |
Reflection shell | Resolution: 2.84→2.96 Å / Redundancy: 6.7 % / Rmerge(I) obs: 1.12 / Mean I/σ(I) obs: 1.77 / % possible all: 95.7 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5D22, 2VGA, 1CQ3 Resolution: 2.845→44.063 Å / SU ML: 0.35 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 26.51 / 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.845→44.063 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Origin x: 40.6418 Å / Origin y: -54.1475 Å / Origin z: -5.9087 Å
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Refinement TLS group | Selection details: all |