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Open data
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Basic information
Entry | Database: PDB / ID: 7uwn | ||||||
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Title | Structure of the IL-17A-IL-17RA-IL-17RC ternary complex | ||||||
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![]() | CYTOKINE / Receptor complex / IL-17A / IL-17RA / IL-17RC | ||||||
Function / homology | ![]() interleukin-17 receptor activity / positive regulation of interleukin-16 production / granulocyte migration / granulocyte chemotaxis / positive regulation of antimicrobial peptide production / Interleukin-17 signaling / T-helper 17 type immune response / intestinal epithelial structure maintenance / negative regulation of inflammatory response to wounding / interleukin-17A-mediated signaling pathway ...interleukin-17 receptor activity / positive regulation of interleukin-16 production / granulocyte migration / granulocyte chemotaxis / positive regulation of antimicrobial peptide production / Interleukin-17 signaling / T-helper 17 type immune response / intestinal epithelial structure maintenance / negative regulation of inflammatory response to wounding / interleukin-17A-mediated signaling pathway / positive regulation of interleukin-23 production / cell death / positive regulation of chemokine (C-X-C motif) ligand 1 production / interleukin-17-mediated signaling pathway / positive regulation of bicellular tight junction assembly / positive regulation of interleukin-13 production / positive regulation of interleukin-5 production / fibroblast activation / positive regulation of osteoclast differentiation / positive regulation of cytokine production involved in inflammatory response / keratinocyte proliferation / cellular response to interleukin-1 / defense response to fungus / coreceptor activity / keratinocyte differentiation / Notch signaling pathway / positive regulation of interleukin-12 production / positive regulation of interleukin-1 beta production / cytokine activity / protein catabolic process / response to virus / response to wounding / positive regulation of inflammatory response / positive regulation of interleukin-6 production / positive regulation of tumor necrosis factor production / cell-cell signaling / gene expression / Interleukin-4 and Interleukin-13 signaling / defense response to Gram-negative bacterium / adaptive immune response / cell surface receptor signaling pathway / defense response to Gram-positive bacterium / inflammatory response / immune response / protein heterodimerization activity / external side of plasma membrane / innate immune response / signaling receptor binding / apoptotic process / SARS-CoV-2 activates/modulates innate and adaptive immune responses / cell surface / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / extracellular space / extracellular region / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.01 Å | ||||||
![]() | Wilson, S.C. / Caveney, N.A. / Jude, K.M. / Garcia, K.C. | ||||||
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![]() | ![]() Title: Organizing structural principles of the IL-17 ligand-receptor axis. Authors: Steven C Wilson / Nathanael A Caveney / Michelle Yen / Christoph Pollmann / Xinyu Xiang / Kevin M Jude / Maximillian Hafer / Naotaka Tsutsumi / Jacob Piehler / K Christopher Garcia / ![]() ![]() Abstract: The IL-17 family of cytokines and receptors have central roles in host defence against infection and development of inflammatory diseases. The compositions and structures of functional IL-17 family ...The IL-17 family of cytokines and receptors have central roles in host defence against infection and development of inflammatory diseases. The compositions and structures of functional IL-17 family ligand-receptor signalling assemblies remain unclear. IL-17E (also known as IL-25) is a key regulator of type 2 immune responses and driver of inflammatory diseases, such as allergic asthma, and requires both IL-17 receptor A (IL-17RA) and IL-17RB to elicit functional responses. Here we studied IL-25-IL-17RB binary and IL-25-IL-17RB-IL-17RA ternary complexes using a combination of cryo-electron microscopy, single-molecule imaging and cell-based signalling approaches. The IL-25-IL-17RB-IL-17RA ternary signalling assembly is a C2-symmetric complex in which the IL-25-IL-17RB homodimer is flanked by two 'wing-like' IL-17RA co-receptors through a 'tip-to-tip' geometry that is the key receptor-receptor interaction required for initiation of signal transduction. IL-25 interacts solely with IL-17RB to allosterically promote the formation of the IL-17RB-IL-17RA tip-to-tip interface. The resulting large separation between the receptors at the membrane-proximal level may reflect proximity constraints imposed by the intracellular domains for signalling. Cryo-electron microscopy structures of IL-17A-IL-17RA and IL-17A-IL-17RA-IL-17RC complexes reveal that this tip-to-tip architecture is a key organizing principle of the IL-17 receptor family. Furthermore, these studies reveal dual actions for IL-17RA sharing among IL-17 cytokine complexes, by either directly engaging IL-17 cytokines or alternatively functioning as a co-receptor. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 279.7 KB | Display | ![]() |
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PDB format | ![]() | 221.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.1 MB | Display | ![]() |
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Full document | ![]() | 1.1 MB | Display | |
Data in XML | ![]() | 53.8 KB | Display | |
Data in CIF | ![]() | 78.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 26837MC ![]() 7uwjC ![]() 7uwkC ![]() 7uwlC ![]() 7uwmC M: map data used to model this data 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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Components
#1: Protein | Mass: 19311.678 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #2: Protein | Mass: 36888.617 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #3: Protein | | Mass: 53294.309 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #4: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #5: Sugar | ChemComp-NAG / Has ligand of interest | N | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: IL-17A-IL-17RA-IL-17RC ternary complex / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: OTHER / Nominal defocus max: 2000 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.01 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 542344 / Symmetry type: POINT | ||||||||||||||||||||||||
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