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Open data
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Basic information
Entry | Database: PDB / ID: 8dpv | ||||||
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Title | The crystal structure of Interleukin-11, W147A mutant | ||||||
![]() | Interleukin-11 | ||||||
![]() | CYTOKINE / complex / IL-6 family cytokine | ||||||
Function / homology | ![]() interleukin-11 receptor binding / megakaryocyte differentiation / negative regulation of hormone secretion / interleukin-11-mediated signaling pathway / IL-6-type cytokine receptor ligand interactions / fat cell differentiation / B cell differentiation / cytokine activity / growth factor activity / positive regulation of peptidyl-tyrosine phosphorylation ...interleukin-11 receptor binding / megakaryocyte differentiation / negative regulation of hormone secretion / interleukin-11-mediated signaling pathway / IL-6-type cytokine receptor ligand interactions / fat cell differentiation / B cell differentiation / cytokine activity / growth factor activity / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of peptidyl-serine phosphorylation / cell population proliferation / positive regulation of MAPK cascade / positive regulation of cell population proliferation / positive regulation of transcription by RNA polymerase II / extracellular space / extracellular region / cytoplasm Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Metcalfe, R.D. / Griffin, M.D.W. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Structures of the interleukin 11 signalling complex reveal gp130 dynamics and the inhibitory mechanism of a cytokine variant. Authors: Riley D Metcalfe / Eric Hanssen / Ka Yee Fung / Kaheina Aizel / Clara C Kosasih / Courtney O Zlatic / Larissa Doughty / Craig J Morton / Andrew P Leis / Michael W Parker / Paul R Gooley / ...Authors: Riley D Metcalfe / Eric Hanssen / Ka Yee Fung / Kaheina Aizel / Clara C Kosasih / Courtney O Zlatic / Larissa Doughty / Craig J Morton / Andrew P Leis / Michael W Parker / Paul R Gooley / Tracy L Putoczki / Michael D W Griffin / ![]() ![]() Abstract: Interleukin (IL-)11, an IL-6 family cytokine, has pivotal roles in autoimmune diseases, fibrotic complications, and solid cancers. Despite intense therapeutic targeting efforts, structural ...Interleukin (IL-)11, an IL-6 family cytokine, has pivotal roles in autoimmune diseases, fibrotic complications, and solid cancers. Despite intense therapeutic targeting efforts, structural understanding of IL-11 signalling and mechanistic insights into current inhibitors are lacking. Here we present cryo-EM and crystal structures of the human IL-11 signalling complex, including the complex containing the complete extracellular domains of the shared IL-6 family β-receptor, gp130. We show that complex formation requires conformational reorganisation of IL-11 and that the membrane-proximal domains of gp130 are dynamic. We demonstrate that the cytokine mutant, IL-11 Mutein, competitively inhibits signalling in human cell lines. Structural shifts in IL-11 Mutein underlie inhibition by altering cytokine binding interactions at all three receptor-engaging sites and abrogating the final gp130 binding step. Our results reveal the structural basis of IL-11 signalling, define the molecular mechanisms of an inhibitor, and advance understanding of gp130-containing receptor complexes, with potential applications in therapeutic development. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 132.9 KB | Display | ![]() |
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PDB format | ![]() | 87.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 434.5 KB | Display | ![]() |
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Full document | ![]() | 436 KB | Display | |
Data in XML | ![]() | 9.7 KB | Display | |
Data in CIF | ![]() | 13 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8dpsC ![]() 8dptC ![]() 8dpuC ![]() 8dpwC ![]() 4mhlS S: Starting model for refinement C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Unit cell |
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Components
#1: Protein | Mass: 18158.158 Da / Num. of mol.: 1 / Mutation: W147A Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Chemical | ChemComp-SO4 / |
#3: Chemical | ChemComp-CL / |
#4: Water | ChemComp-HOH / |
Has ligand of interest | N |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 1.92 Å3/Da / Density % sol: 36.08 % / Description: plates |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 8.5 Details: PEG 3350, 200 mM ammonium sulphate, 100 mM Tris pH 8.5 |
-Data collection
Diffraction | Mean temperature: 100 K / Ambient temp details: liquid nitrogen / Serial crystal experiment: N |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Oct 20, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9537 Å / Relative weight: 1 |
Reflection | Resolution: 1.48→44.67 Å / Num. obs: 24354 / % possible obs: 100 % / Redundancy: 12.9 % / Biso Wilson estimate: 23.39 Å2 / CC1/2: 0.999 / Rpim(I) all: 0.034 / Rrim(I) all: 0.089 / Rsym value: 0.082 / Net I/σ(I): 12.9 |
Reflection shell | Resolution: 1.48→1.51 Å / Mean I/σ(I) obs: 1.3 / Num. unique obs: 1182 / CC1/2: 0.59 / Rpim(I) all: 0.743 / Rrim(I) all: 2.003 / Rsym value: 1.859 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 4MHL Resolution: 1.48→37.01 Å / SU ML: 0.1497 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 21.2089 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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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: 38.47 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.48→37.01 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: -3.78212012334 Å / Origin y: 18.345556782 Å / Origin z: -6.14215689752 Å
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Refinement TLS group | Selection details: (chain 'A' and resid 10 through 178) |