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Open data
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Basic information
Entry | Database: PDB / ID: 8ppm | |||||||||
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Title | IL-12Rb1 neutralizing Fab4, crystal kappa variant | |||||||||
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![]() | IMMUNOSUPPRESSANT / antibody / Fab fragment / designed crystal contact | |||||||||
Function / homology | : ![]() | |||||||||
Biological species | ![]() | |||||||||
Method | ![]() ![]() ![]() | |||||||||
![]() | 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 | ![]() | 218 KB | Display | ![]() |
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PDB format | ![]() | 144.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 431.4 KB | Display | ![]() |
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Full document | ![]() | 431.2 KB | Display | |
Data in XML | ![]() | 18 KB | Display | |
Data in CIF | ![]() | 25.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8c7mC ![]() 8cr5C ![]() 8cr6C ![]() 8cr8C ![]() 8odxC ![]() 8odzC ![]() 8oe0C ![]() 8oe4C ![]() 8pb1C 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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Unit cell |
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Components
#1: Antibody | Mass: 24786.586 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: resideus [225-] (GHHHHHH) encode cloning scar and purification tag. Tag was not removed prior to crystallization. Source: (gene. exp.) ![]() Cell line: HEK293S MGAT-/- / Plasmid: pHLsec / Production host: ![]() | ||||
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#2: Antibody | Mass: 23239.732 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Plasmid: pHLsec / Cell line (production host): HEK293S MGAT-/- / Production host: ![]() | ||||
#3: Chemical | #4: Water | ChemComp-HOH / | Has ligand of interest | N | |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.63 Å3/Da / Density % sol: 53.3 % |
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Crystal grow | Temperature: 287 K / Method: vapor diffusion, sitting drop Details: Fab4 dissociated from target in crystallization drop. |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||
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Diffraction source | Source: ![]() ![]() ![]() | ||||||||||||||||||||||||||||
Detector | Type: DECTRIS EIGER2 X CdTe 16M / Detector: PIXEL / Date: Apr 24, 2023 | ||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9763 Å / Relative weight: 1 | ||||||||||||||||||||||||||||
Reflection | Resolution: 2.03→163.83 Å / Num. obs: 31735 / % possible obs: 97 % / Redundancy: 18.71 % / Biso Wilson estimate: 39.95 Å2 / CC1/2: 0.999 / Rrim(I) all: 0.11 / Net I/σ(I): 18.38 | ||||||||||||||||||||||||||||
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: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 46.63 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.03→62.41 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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