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Open data
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Basic information
Entry | Database: PDB / ID: 8cr6 | |||||||||
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Title | mouse Interleukin-12 | |||||||||
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![]() | CYTOKINE / inflammation / immunity / heterodimer | |||||||||
Function / homology | ![]() interleukin-12 beta subunit binding / Interleukin-12 signaling / Interleukin-23 signaling / interleukin-23 receptor binding / Interleukin-35 Signalling / interleukin-12 alpha subunit binding / interleukin-12 complex / interleukin-23 complex / T-helper 1 cell activation / natural killer cell activation involved in immune response ...interleukin-12 beta subunit binding / Interleukin-12 signaling / Interleukin-23 signaling / interleukin-23 receptor binding / Interleukin-35 Signalling / interleukin-12 alpha subunit binding / interleukin-12 complex / interleukin-23 complex / T-helper 1 cell activation / natural killer cell activation involved in immune response / positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target / negative regulation of vascular endothelial growth factor signaling pathway / negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis / positive regulation of T-helper 1 type immune response / positive regulation of smooth muscle cell apoptotic process / interleukin-12 receptor binding / natural killer cell activation / T-helper cell differentiation / positive regulation of osteoclast differentiation / negative regulation of interleukin-17 production / positive regulation of NK T cell proliferation / interleukin-12-mediated signaling pathway / response to UV-B / positive regulation of natural killer cell proliferation / positive regulation of granulocyte macrophage colony-stimulating factor production / positive regulation of T cell differentiation / cytokine receptor activity / negative regulation of interleukin-10 production / positive regulation of activated T cell proliferation / defense response to protozoan / positive regulation of interleukin-17 production / positive regulation of interleukin-10 production / immunoglobulin mediated immune response / negative regulation of protein secretion / T cell proliferation / positive regulation of T cell proliferation / positive regulation of tyrosine phosphorylation of STAT protein / negative regulation of inflammatory response to antigenic stimulus / positive regulation of defense response to virus by host / positive regulation of interleukin-12 production / : / cytokine activity / endosome lumen / negative regulation of smooth muscle cell proliferation / growth factor activity / cytokine-mediated signaling pathway / cellular response to type II interferon / Golgi lumen / positive regulation of T cell mediated cytotoxicity / positive regulation of tumor necrosis factor production / positive regulation of type II interferon production / cell migration / cellular response to lipopolysaccharide / defense response to Gram-negative bacterium / defense response to virus / cell population proliferation / cell surface receptor signaling pathway / immune response / protein heterodimerization activity / endoplasmic reticulum lumen / external side of plasma membrane / protein-containing complex binding / cell surface / extracellular space / extracellular region / identical protein binding / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ![]() ![]() ![]() | |||||||||
![]() | Merceron, R. / Felix, J. / Lambert, E. / Bloch, Y. / Savvides, S.N. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structures of complete extracellular receptor assemblies mediated by IL-12 and IL-23. Authors: Yehudi Bloch / Jan Felix / Romain Merceron / Mathias Provost / Royan Alipour Symakani / Robin De Backer / Elisabeth Lambert / Ahmad R Mehdipour / Savvas N Savvides / ![]() ![]() ![]() ![]() Abstract: Cell-surface receptor complexes mediated by pro-inflammatory interleukin (IL)-12 and IL-23, both validated therapeutic targets, are incompletely understood due to the lack of structural insights into ...Cell-surface receptor complexes mediated by pro-inflammatory interleukin (IL)-12 and IL-23, both validated therapeutic targets, are incompletely understood due to the lack of structural insights into their complete extracellular assemblies. Furthermore, there is a paucity of structural details describing the IL-12-receptor interaction interfaces, in contrast to IL-23-receptor complexes. Here we report structures of fully assembled mouse IL-12/human IL-23-receptor complexes comprising the complete extracellular segments of the cognate receptors determined by electron cryo-microscopy. The structures reveal key commonalities but also surprisingly diverse features. Most notably, whereas IL-12 and IL-23 both utilize a conspicuously presented aromatic residue on their α-subunit as a hotspot to interact with the N-terminal Ig domain of their high-affinity receptors, only IL-12 juxtaposes receptor domains proximal to the cell membrane. Collectively, our findings will help to complete our understanding of cytokine-mediated assemblies of tall cytokine receptors and will enable a cytokine-specific interrogation of IL-12/IL-23 signaling in physiology and disease. | |||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 228.9 KB | Display | ![]() |
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PDB format | ![]() | 162.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 758.6 KB | Display | ![]() |
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Full document | ![]() | 762.1 KB | Display | |
Data in XML | ![]() | 17.6 KB | Display | |
Data in CIF | ![]() | 23.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8c7mC ![]() 8cr5C ![]() 8cr8C ![]() 8odxC ![]() 8odzC ![]() 8oe0C ![]() 8oe4C ![]() 8pb1C ![]() 8ppmC C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 38282.391 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: [M1-A22] encode the signal peptide and are most likely removed during translation/folding. Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein | Mass: 28403.510 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: Residues [1-22] encode the signal peptide which is most likely removed during translation/folding. Residues [216-253] encode cloning scar, protease site, avi-tag and his-tag. Residues [224- ...Details: Residues [1-22] encode the signal peptide which is most likely removed during translation/folding. Residues [216-253] encode cloning scar, protease site, avi-tag and his-tag. Residues [224-253] are most likely removed due to protease treatment. Source: (gene. exp.) ![]() ![]() ![]() |
#3: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
#4: Sugar | ChemComp-NAG / |
#5: Water | ChemComp-HOH / |
Has ligand of interest | N |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2 Å3/Da / Density % sol: 38.42 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop Details: JCSG-plus G4: 0.2 M TMAO, 0.1 M Tris pH 8.5, 20% w/v/ PEG 2000 MME, 20 mM BaCl2 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: ![]() ![]() ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jul 22, 2017 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1.008 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.85→47.34 Å / Num. obs: 12530 / % possible obs: 96.1 % / Redundancy: 2.91 % / Biso Wilson estimate: 97.92 Å2 / CC1/2: 0.999 / Rrim(I) all: 0.058 / Net I/σ(I): 13.9 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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Processing
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Refinement | Method to determine structure: ![]() 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: 110.55 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.85→47.34 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 | Refine-ID: X-RAY DIFFRACTION
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